Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive mol...Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.展开更多
Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,lim...Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.展开更多
Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are des...Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.展开更多
The phenomenon of pyroptosis has gained increasing prominence in recent decades as a significant contributor to cellular mortality.The process of pyroptosis plays a crucial role in the regulation of various types of c...The phenomenon of pyroptosis has gained increasing prominence in recent decades as a significant contributor to cellular mortality.The process of pyroptosis plays a crucial role in the regulation of various types of cancers.The induction of pyroptosis can be achieved through various mechanisms,including the activation of small molecule pyrogen inducers.The use of.small molecule pyrogen inducer alone,however,has limitations.On one hand,we benefit from the utilization of nano delivery systems(NDS).On the other hand,there is an enhanced comprehension of the underlying mechanism governing pyroptosis.A novel therapeutic strategy,resulting from a clever amalgamation of the two approaches,has demonstrated significant efficacy in experimental treatment of certain diseases.A variety of nanocarriers,including liposomes,hydrogels,polymer micelles,exosomes,metal-organic frameworks protein nanoparticles,cell membrane biomimetic nanocarriers,carbon nanotubes,dendrimers,polymer conjugates and polymer nanoparticles are utilized for the delivery of drugs that induce pyroptosis in cells.By integrating the aforementioned approaches,a diverse range of pyroptosis strategies have been developed utilizing NDS,encompassing stem cell targeting,disruption of ion homeostasis,augmentation of reactive oxygen species generation,induction of epigenetic modifications,and transportation of gaseous protein gasdermins family proteins.However,the clinical application of these strategies still encounters numerous challenges that need to be addressed,including limited comprehension of NDS,incomplete understanding of the interaction mechanisms between nanomaterials and biological systems,and insufficient knowledge regarding nanocarrier materials.In this study,we aim to advance the field of pyroptosis in cancer treatment.The induction of pyroptotic cell death is believed to hold great promise as an ideal therapeutic approach for the management,regulation,and treatment of numerous types of cancers.展开更多
Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge si...Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.展开更多
In recent years, robots used for targeted drug delivery in the stomach have received extensive attention. Inspired by tumbleweeds, we have designed a dual-responsive soft robot based on poly(N‑isopropylacrylamide) and...In recent years, robots used for targeted drug delivery in the stomach have received extensive attention. Inspired by tumbleweeds, we have designed a dual-responsive soft robot based on poly(N‑isopropylacrylamide) and MoS_(2). Under the action of an adjustable magnetic field, it can achieve steady motion at a frequency that allows it to move up to 35 mm/s, demonstrating high flexibility and controllability. It can also roll along a predetermined path, traverse mazes, climb over obstacles, among other functions. In addition, by harnessing the photothermal conversion effect of MoS_(2), the robot can be opened and closed using light, enabling controlled drug release. Targeted drug delivery is achieved in a gastric model using our designed soft robot, marking a significant clinical advancement expected to revolutionize future medical treatments and enhance the efficacy of drug therapy.展开更多
Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation...Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.展开更多
Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of ther...Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging.Nanomedicine is designed and has significantly impacted the scientific community.Over the last few decades,to address the shortcomings of synthetic nanoparticles,a new approach has emerged that mimic the physiological environment.Cell membrane-coated nanoparticles have been developed to interact with the physiological environment,enhance central nervous system drug delivery and mask toxic effects.Cell membranes are multifunctional,biocompatible platforms with the potential for surface modification and targeted delivery design.A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics,which can improve the BBB recognition and transport.This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them.Moreover,major cell membranes used in biomedical applications are discussed with a focus on PD.展开更多
As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is...As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.展开更多
The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can...The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.展开更多
Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic dru...Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic drugs with minimal side effects[1].Recently,natural medicine has garnered significant attention due to its remarkable efficacy and limited side effects.Icariin,a naturally occurring flavonoid,exhibits excellent potential as a therapeutic agent for neurodegenerative disease[2].However,its clinical application is limited by poor water solubility,low bioavailability,and high clearance rates.Here,an aqueous formulation of icariin/hydroxypropyl-β-cyclodextrin(HP-β-CD)supramolecular inclusion complex was obtained to optimize icariin properties.Furthermore,icariin cyclodextrin supramolecular inclusion complex based thermosensitive(icariin gels)was innovated.At lower temperatures,it remained in a liquid phase with high fluidity.Upon reaching the gelation temperature,it underwent a transition to a gel phase with significantly reduced fluidity,which may be suitable for the design of an intranasal delivery system for PD treatment.The innovative approach capitalizes on the exceptional characteristics of HP-β-CD,which was utilized to synergize with nasal delivery for targeted brain delivery and with icariin for PD treatment[3,4].展开更多
MXene-based smart contact lenses demonstrate a cutting-edge advancement in wearable ophthalmic technology,combining real-time biosensing,therapeutic capabilities,and user comfort in a single platform.These devices tak...MXene-based smart contact lenses demonstrate a cutting-edge advancement in wearable ophthalmic technology,combining real-time biosensing,therapeutic capabilities,and user comfort in a single platform.These devices take the advantage of the exceptional electrical conductivity,mechanical flexibility,and biocompatibility of two-dimensional MXenes to enable noninvasive,tear-based monitoring of key physiological markers such as intraocular pressure and glucose levels.Recent developments focus on the integration of transparent MXene films into the conventional lens materials,allowing multifunctional performance including photothermal therapy,antimicrobial and anti-inflammation protection,and dehydration resistance.These innovations offer promising strategies for ocular disease management and eye protection.In addition to their multifunctionality,improvements in MXene synthesis and device engineering have enhanced the stability,transparency,and wearability of these lenses.Despite these advances,challenges remain in long-term biostability,scalable production,and integration with wireless communication systems.This review summarizes the current progress,key challenges,and future directions of MXene-based smart contact lenses,highlighting their transformative potential in next-generation digital healthcare and ophthalmic care.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and pro...The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and properties,it has resulted in the development of various particle sizes and shapes of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials.This has led to the extension of the uses of the materials to photocatalysis,drug delivery,and CT image contrast agents.Accordingly,these applications have been compiled and discussed in depth in this review.The potential of these materials in the above applications has started to attract significant attention.Moreover,the compilation of in-vitro toxicity studies from the literature was also discussed to facilitate the biocompatibility of the developed Gd(OH)_(3)nanomaterials.However,despite the rapid progress of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials,there are still knowledge gaps in certain areas.Therefore,this review provides insights into the recent development of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials to aid in accelerating novel developments.展开更多
Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular pro...Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
Functional neurological recovery remains the primary objective when treating ischemic stroke.However,current therapeutic approaches often fall short of achieving optimal outcomes.One of the most significant challenges...Functional neurological recovery remains the primary objective when treating ischemic stroke.However,current therapeutic approaches often fall short of achieving optimal outcomes.One of the most significant challenges in stroke treatment is the effective delivery of neuroprotective agents across the blood–brain barrier to ischemic regions within the brain.The blood–brain barrier,while essential for protecting the brain from harmful substances,also restricts the passage of many therapeutic compounds,thus limiting their efficacy.In this review,we summarizes the emerging role of nanoparticle-based therapies for the treatment of ischemic stroke and investigate their potential to revolutionize drug delivery,enhance neuroprotection,and promote functional recovery.Recent advancements in nanotechnology have led to the development of engineered nanoparticles specifically designed to overcome the blood–brain barrier,thus enabling the targeted delivery of therapeutic agents directly to the affected brain areas.Preclinical studies have demonstrated the remarkable potential of nanoparticle-based therapies to activate key neuroprotective pathways,such as the phosphoinositide 3-kinase/protein kinase B/c AMP response element-binding protein signaling cascade,which is crucial for neuronal survival,synaptic plasticity,and post-stroke recovery.By modulating these pathways,nanoparticles could mitigate neuronal damage,reduce inflammation,and promote tissue repair.Furthermore,nanoparticles offer a unique advantage by enabling multimodal therapeutic strategies that simultaneously target multiple pathological mechanisms of ischemic stroke,including oxidative stress,neuroinflammation,and apoptosis.This multifaceted approach enhances the overall efficacy of treatment,addressing the complex and interconnected processes that contribute to stroke-related brain injury.Surface modifications,such as functionalization with specific ligands or targeting molecules,further improve the precision of drug delivery,enhance targeting specificity,and prolong systemic circulation,thereby optimizing therapeutic outcomes.Nanoparticlebased therapeutics represent a paradigm shift for the management of stroke and provide a promising avenue for reducing post-stroke disability and improving the outcomes of long-term rehabilitation.By combining targeted drug delivery with the ability to modulate critical neuroprotective pathways,nanoparticles hold the potential to transform the treatment landscape for ischemic stroke.However,while preclinical data are highly encouraging,significant challenges remain in translating these advancements into clinical practice.Further research is needed to refine nanoparticle designs,optimize their safety profiles,and ensure their scalability for widespread application.Rigorous clinical trials are essential to validate their efficacy,assess long-term biocompatibility,and address potential off-target effects.The integration of interdisciplinary approaches,combining insights from nanotechnology,neuroscience,and pharmacology,will be critical if we are to overcome these challenges.Ultimately,nanoparticle-based therapies offer a foundation for innovative,precision-based treatments that could significantly improve outcomes for stroke patients,thus paving the way for a new era in stroke care and neurological rehabilitation.展开更多
Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating ga...Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.展开更多
The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, p...The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.展开更多
RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, p...RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.展开更多
基金supported by the National Natural Science Foundation of China(51925304)Natural Science Foundation of Sichuan Province(2024NSFSC1023)Medical Research Program of Sichuan Province(Q23015).
文摘Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone regeneration.However,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in vivo.Hydrogels have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological conditions.This review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying diseases.Additionally,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential delivery.Finally,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.
基金supported by the National Natural Science Foundation of China(No.52105072)Zhejiang Provincial Natural Science Foundation of China(No.LZ24E050004)+2 种基金Jiangsu Provincial Outstanding Youth Program(No.BK20230072)a grant from Suzhou Industrial Foresight and Key Core Technology Project(No.SYC2022044)grants from Jiangsu Qinglan Project and Jiangsu 333 High-level Talents.
文摘Wireless capsule endoscopy(WCE)has the potential to fully replace conventional wired counterparts for its low invasiveness.Recent studies have attempted to expand the functions of capsules toward this goal.However,limitations in space and energy supply have resulted in the inability to perform multiple diagnostic and treatment tasks using a single capsule.In this study,we developed a dual-functional capsule robot(DFCR)for drug delivery and tissue biopsy based on magnetic torsion spring technology.The delivery module was shown to rotate the push rod with a thrust of 894 mN to release approximately 0.3 mL of semisolid drug.The biopsy module used a built-in blade to cut tissue with a shear stress of 22.87 MPa,producing a sample of approximately 1.8 mm3.Additionally,a five-degree-of-freedom permanent magnet drive system was developed.By adjusting the strength of the unidirectional magnetic field generated by an external magnet,the capsule can be wirelessly controlled to sequentially trigger the two functions.Ex vivo tests on porcine stomachs confirmed the feasibility of the prototype capsule(12 mm in diameter and 45 mm in length)in active movement,medication,and tissue biopsy.The newly developed DFCR further expands the clinical application prospects of WCE robots in minimally invasive surgery.
文摘Nanotechnology in cancer therapy has significantly advanced treatment precision,effectiveness,and safety,improving patient outcomes and personalized care.Engineered smart nanoparticles and cell-based therapies are designed to target tumor cells,precisely sensing the tumor microenvironment(TME)and sparing normal cells.These nanoparticles enhance drug accumulation in tumors by solubilizing insoluble compounds or preventing their degradation,and they can also overcome therapy resistance and deliver multiple drugs simultaneously.Despite these benefits,challenges remain in patient-specific responses and regulatory approvals for cell-based or nanoparticle therapies.Cell-based drug delivery systems(DDSs)that primarily utilize the immune-recognition principle between ligands and receptors have shown promise in selectively targeting and destroying cancer cells.This review aims to provide a comprehensive overview of various nanoparticle and cell-based drug delivery system types used in cancer research.It covers approved and experimental nanoparticle therapies,including liposomes,micelles,protein-based and polymeric nanoparticles,as well as cell-based DDSs like macrophages,T-lymphocytes,dendritic cells,viruses,bacterial ghosts,minicells,SimCells,and outer membrane vesicles(OMVs).The review also explains the role of TME and its impact on developing smart DDSs in combination therapies and integrating nanoparticles with cell-based systems for targeting cancer cells.By detailing DDSs at different stages of development,from laboratory research to clinical trials and approved treatments,this review provides the latest insights and a collection of valuable citations of the innovative strategies that can be improved for the precise treatment of cancer.
文摘The phenomenon of pyroptosis has gained increasing prominence in recent decades as a significant contributor to cellular mortality.The process of pyroptosis plays a crucial role in the regulation of various types of cancers.The induction of pyroptosis can be achieved through various mechanisms,including the activation of small molecule pyrogen inducers.The use of.small molecule pyrogen inducer alone,however,has limitations.On one hand,we benefit from the utilization of nano delivery systems(NDS).On the other hand,there is an enhanced comprehension of the underlying mechanism governing pyroptosis.A novel therapeutic strategy,resulting from a clever amalgamation of the two approaches,has demonstrated significant efficacy in experimental treatment of certain diseases.A variety of nanocarriers,including liposomes,hydrogels,polymer micelles,exosomes,metal-organic frameworks protein nanoparticles,cell membrane biomimetic nanocarriers,carbon nanotubes,dendrimers,polymer conjugates and polymer nanoparticles are utilized for the delivery of drugs that induce pyroptosis in cells.By integrating the aforementioned approaches,a diverse range of pyroptosis strategies have been developed utilizing NDS,encompassing stem cell targeting,disruption of ion homeostasis,augmentation of reactive oxygen species generation,induction of epigenetic modifications,and transportation of gaseous protein gasdermins family proteins.However,the clinical application of these strategies still encounters numerous challenges that need to be addressed,including limited comprehension of NDS,incomplete understanding of the interaction mechanisms between nanomaterials and biological systems,and insufficient knowledge regarding nanocarrier materials.In this study,we aim to advance the field of pyroptosis in cancer treatment.The induction of pyroptotic cell death is believed to hold great promise as an ideal therapeutic approach for the management,regulation,and treatment of numerous types of cancers.
基金supported by the Individual Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)through the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
基金the financial support through National Natural Science Foundation of China(Project No.62273289)The Youth Innovation Science and Technology Support Program of Shandong Province(Project No.2022KJ274)+1 种基金Shandong Provincial Natural Science Foundation(ZR2024MF007)Graduate Innovation Foundation of Yantai University,GIFYTU.
文摘In recent years, robots used for targeted drug delivery in the stomach have received extensive attention. Inspired by tumbleweeds, we have designed a dual-responsive soft robot based on poly(N‑isopropylacrylamide) and MoS_(2). Under the action of an adjustable magnetic field, it can achieve steady motion at a frequency that allows it to move up to 35 mm/s, demonstrating high flexibility and controllability. It can also roll along a predetermined path, traverse mazes, climb over obstacles, among other functions. In addition, by harnessing the photothermal conversion effect of MoS_(2), the robot can be opened and closed using light, enabling controlled drug release. Targeted drug delivery is achieved in a gastric model using our designed soft robot, marking a significant clinical advancement expected to revolutionize future medical treatments and enhance the efficacy of drug therapy.
基金sponsored by the Fundamental Research Funds forthe Central Universities(No.2024-JYB-JBZD-047)High Level Key Discipline Construction of Traditional Chinese Medicine(zyyzdxk-2023272).
文摘Background:Building upon our previous work that developed a folate receptor-mediated,euphaorbia factor L1-loaded PLGA microsphere system integrating active and magnetic targeting for theranostics,further investigation into its in vivo pharmacokinetics and tissue distribution is warranted despite its demonstrated biocompatibility and safety.Methods:A UPLC-MS/MS method was established to determine the concentration of euphorbia sterol in rat plasma and mouse tissue homogenates,healthy male SD rats and KM mice were administered in groups,drug concentrations at different time points were determined,pharmacokinetic parameters were analyzed by DAS software,and data were processed by SAS software.Results:The proposed method met the requirements of biological sample detection.The plasma pharmacokinetics of rats showed that the drug concentration in the microsphere group was lower than that in the injection group,and the parameters such as mean residence time(MRT(0–t)),half-life(T1/2z)and apparent volume of distribution(Vz)were significantly different from those in the solution group.The distribution of mouse tissues showed that the drug concentrations in the liver and lung tissues of the microsphere preparation group were higher than those in the injection group,and the drug concentrations in the lung and liver tissues were more distributed.Conclusion:The targeted drug delivery system changed the pharmacokinetic behavior and tissue distribution of euphorbia sterol,slowed down plasma elimination,prolonged the half-life,and improved the targeting of drugs in lung and liver tissues and the magnetic targeting effect of lungs.
基金Department of Pharmaceuticals,Ministry of Chemicals and Fertilizers,Centre of Excellence(CoE),NDDS,NIPER-Raebareli.Communication Number/737。
文摘Neuroinflammation,α-synuclein pathology and dopaminergic cell loss are the hallmarks of Parkinson’s disease(PD),an incurable movement disorder.The presence of the blood-brain barrier(BBB)impedes the delivery of therapeutics and makes the design of drug-targeting delivery vehicles challenging.Nanomedicine is designed and has significantly impacted the scientific community.Over the last few decades,to address the shortcomings of synthetic nanoparticles,a new approach has emerged that mimic the physiological environment.Cell membrane-coated nanoparticles have been developed to interact with the physiological environment,enhance central nervous system drug delivery and mask toxic effects.Cell membranes are multifunctional,biocompatible platforms with the potential for surface modification and targeted delivery design.A synchronous design of cell membrane and nanoparticles is required for the cell membrane-based biomimetics,which can improve the BBB recognition and transport.This review summarizes the challenges in drug delivery and how cell membrane-coated nanoparticles can overcome them.Moreover,major cell membranes used in biomedical applications are discussed with a focus on PD.
基金supported by the National Key R&D Program of China(No.2020YFE0201700)the Liaoning Revitalization Talents Program(No.XLYC1908031)。
文摘As one of the most common gynecological malignancies,peritoneal metastasis is a common feature and cause of high mortality in ovarian cancer(OC).Currently,the standard treatment for OC and its peritoneal metastasis is maximal cytoreductive surgery(CRS)combined with platinum-based chemotherapy.Compared with intravenous chemotherapy,traditional intraperitoneal(IP)chemotherapy exhibits obvious pharmacokinetic(PK)advantages and systemic safety and has shown significant survival benefits in several clinical studies of OC patients.However,there remain several challenges in traditional IP chemotherapy,such as insufficient drug retention,a lack of tumor targeting,inadequate drug penetration,gastrointestinal toxicity,and limited inhibition of tumor metastasis and chemoresistance.Nanomedicine-based IP targeting delivery systems,through specific drug carrier design with tumor cells and tumor environment(TME)targeting,make it possible to overcome these challenges and maximize local therapy efficacy while reducing side effects.In this review article,the rationale and challenges of nanomedicine-based IP chemotherapies,as well as their in vivo fate after IP administration,which are crucial for their rational design and clinical translation,are firstly discussed.Then,current strategies for nanomedicine-based targeting delivery systems and the relevant clinical trials in IP chemotherapy are summarized.Finally,the future directions of the nanomedicine-based IP targeting delivery system for OC and its peritoneal metastasis are proposed,expecting to improve the clinical development of IP chemotherapy.
基金Hongguang Wu,Both authors contributed equally to this work and share first authorshipLing Dong,Both authors contributed equally to this work and share first authorship。
文摘The human retina,a complex and highly specialized structure,includes multiple cell types that work synergistically to generate and transmit visual signals.However,genetic predisposition or age-related degeneration can lead to retinal damage that severely impairs vision or causes blindness.Treatment options for retinal diseases are limited,and there is an urgent need for innovative therapeutic strategies.Cell and gene therapies are promising because of the efficacy of delivery systems that transport therapeutic genes to targeted retinal cells.Gene delivery systems hold great promise for treating retinal diseases by enabling the targeted delivery of therapeutic genes to affected cells or by converting endogenous cells into functional ones to facilitate nerve regeneration,potentially restoring vision.This review focuses on two principal categories of gene delivery vectors used in the treatment of retinal diseases:viral and non-viral systems.Viral vectors,including lentiviruses and adeno-associated viruses,exploit the innate ability of viruses to infiltrate cells,which is followed by the introduction of therapeutic genetic material into target cells for gene correction.Lentiviruses can accommodate exogenous genes up to 8 kb in length,but their mechanism of integration into the host genome presents insertion mutation risks.Conversely,adeno-associated viruses are safer,as they exist as episomes in the nucleus,yet their limited packaging capacity constrains their application to a narrower spectrum of diseases,which necessitates the exploration of alternative delivery methods.In parallel,progress has also occurred in the development of novel non-viral delivery systems,particularly those based on liposomal technology.Manipulation of the ratios of hydrophilic and hydrophobic molecules within liposomes and the development of new lipid formulations have led to the creation of advanced non-viral vectors.These innovative systems include solid lipid nanoparticles,polymer nanoparticles,dendrimers,polymeric micelles,and polymeric nanoparticles.Compared with their viral counterparts,non-viral delivery systems offer markedly enhanced loading capacities that enable the direct delivery of nucleic acids,mRNA,or protein molecules into cells.This bypasses the need for DNA transcription and processing,which significantly enhances therapeutic efficiency.Nevertheless,the immunogenic potential and accumulation toxicity associated with non-viral particulate systems necessitates continued optimization to reduce adverse effects in vivo.This review explores the various delivery systems for retinal therapies and retinal nerve regeneration,and details the characteristics,advantages,limitations,and clinical applications of each vector type.By systematically outlining these factors,our goal is to guide the selection of the optimal delivery tool for a specific retinal disease,which will enhance treatment efficacy and improve patient outcomes while paving the way for more effective and targeted therapeutic interventions.
基金supported by the National Natural Science Foundation of China(Grant No.:82104399)the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,China(Grant No.:22HHZYSS00001).
文摘Parkinson's disease(PD)is a debilitating and progressive neurodegenerative disorder with complex pathology and multiple membrane barriers that hinder drug delivery,resulting in the absence of ideal therapeutic drugs with minimal side effects[1].Recently,natural medicine has garnered significant attention due to its remarkable efficacy and limited side effects.Icariin,a naturally occurring flavonoid,exhibits excellent potential as a therapeutic agent for neurodegenerative disease[2].However,its clinical application is limited by poor water solubility,low bioavailability,and high clearance rates.Here,an aqueous formulation of icariin/hydroxypropyl-β-cyclodextrin(HP-β-CD)supramolecular inclusion complex was obtained to optimize icariin properties.Furthermore,icariin cyclodextrin supramolecular inclusion complex based thermosensitive(icariin gels)was innovated.At lower temperatures,it remained in a liquid phase with high fluidity.Upon reaching the gelation temperature,it underwent a transition to a gel phase with significantly reduced fluidity,which may be suitable for the design of an intranasal delivery system for PD treatment.The innovative approach capitalizes on the exceptional characteristics of HP-β-CD,which was utilized to synergize with nasal delivery for targeted brain delivery and with icariin for PD treatment[3,4].
文摘MXene-based smart contact lenses demonstrate a cutting-edge advancement in wearable ophthalmic technology,combining real-time biosensing,therapeutic capabilities,and user comfort in a single platform.These devices take the advantage of the exceptional electrical conductivity,mechanical flexibility,and biocompatibility of two-dimensional MXenes to enable noninvasive,tear-based monitoring of key physiological markers such as intraocular pressure and glucose levels.Recent developments focus on the integration of transparent MXene films into the conventional lens materials,allowing multifunctional performance including photothermal therapy,antimicrobial and anti-inflammation protection,and dehydration resistance.These innovations offer promising strategies for ocular disease management and eye protection.In addition to their multifunctionality,improvements in MXene synthesis and device engineering have enhanced the stability,transparency,and wearability of these lenses.Despite these advances,challenges remain in long-term biostability,scalable production,and integration with wireless communication systems.This review summarizes the current progress,key challenges,and future directions of MXene-based smart contact lenses,highlighting their transformative potential in next-generation digital healthcare and ophthalmic care.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
基金the FRC grant(UBD/RSCH/1.4/FICBF(b)/2023/059)received from Universiti Brunei Darussalam,Brunei Darussalam。
文摘The syntheses of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials have been reported and these materials have been developed as excellent MRI contrast agents.Due to the close interrelation between their morphology and properties,it has resulted in the development of various particle sizes and shapes of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials.This has led to the extension of the uses of the materials to photocatalysis,drug delivery,and CT image contrast agents.Accordingly,these applications have been compiled and discussed in depth in this review.The potential of these materials in the above applications has started to attract significant attention.Moreover,the compilation of in-vitro toxicity studies from the literature was also discussed to facilitate the biocompatibility of the developed Gd(OH)_(3)nanomaterials.However,despite the rapid progress of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials,there are still knowledge gaps in certain areas.Therefore,this review provides insights into the recent development of Gd(OH)_(3)and Gd(OH)_(3)-based nanomaterials to aid in accelerating novel developments.
基金supported by the Russian state-funded project for ICBFM SB RAS(grant number 125012300656-5)。
文摘Background:The development of materials for cardiovascular surgery that would improve the effectiveness of surgical interventions remains an important task.Surgical intervention during the implantation of vascular prostheses and stents,and the body’s reaction to artificial materials,could lead to chronic inflammation,a local increase in the concentration of proinflammatory factors,and stimulation of unwanted tissue growth.The introduction of nonsteroidal anti-inflammatory drugs into implantable devices could be used to obtain vascular implants that do not induce inflammation and do not induce neointimal tissue outgrowth.Methods:The scaffolds were made by electrospinning from mixtures of polyurethane(PU)with diclofenac(DF).The kinetics of DF release from the scaffolds composed of 3%PU/10%HSA/3%DMSO/DF and 3%PU/DF were studied.The biocompatibility and anti-inflammatory effects of the obtained scaffolds on human gingival fibroblasts and umbilical vein endothelial cells were studied.Results:Both types of scaffolds are characterized by fast DF release.The viability of cells cultured on scaffolds is 2 times worse than that of cells cultured on plastic.The level of the proinflammatory cytokine IL-6 in the culture medium of cells cultured on DF-containing scaffolds was lower than that of cells cultured on scaffolds without DF.Conclusion:The introduction of DF into scaffolds minimizes the inflammation caused by cell reactions to an artificial material.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
基金supported by the National Natural Science Foundations of China,Nos.82272163,82472164(both MF)。
文摘Functional neurological recovery remains the primary objective when treating ischemic stroke.However,current therapeutic approaches often fall short of achieving optimal outcomes.One of the most significant challenges in stroke treatment is the effective delivery of neuroprotective agents across the blood–brain barrier to ischemic regions within the brain.The blood–brain barrier,while essential for protecting the brain from harmful substances,also restricts the passage of many therapeutic compounds,thus limiting their efficacy.In this review,we summarizes the emerging role of nanoparticle-based therapies for the treatment of ischemic stroke and investigate their potential to revolutionize drug delivery,enhance neuroprotection,and promote functional recovery.Recent advancements in nanotechnology have led to the development of engineered nanoparticles specifically designed to overcome the blood–brain barrier,thus enabling the targeted delivery of therapeutic agents directly to the affected brain areas.Preclinical studies have demonstrated the remarkable potential of nanoparticle-based therapies to activate key neuroprotective pathways,such as the phosphoinositide 3-kinase/protein kinase B/c AMP response element-binding protein signaling cascade,which is crucial for neuronal survival,synaptic plasticity,and post-stroke recovery.By modulating these pathways,nanoparticles could mitigate neuronal damage,reduce inflammation,and promote tissue repair.Furthermore,nanoparticles offer a unique advantage by enabling multimodal therapeutic strategies that simultaneously target multiple pathological mechanisms of ischemic stroke,including oxidative stress,neuroinflammation,and apoptosis.This multifaceted approach enhances the overall efficacy of treatment,addressing the complex and interconnected processes that contribute to stroke-related brain injury.Surface modifications,such as functionalization with specific ligands or targeting molecules,further improve the precision of drug delivery,enhance targeting specificity,and prolong systemic circulation,thereby optimizing therapeutic outcomes.Nanoparticlebased therapeutics represent a paradigm shift for the management of stroke and provide a promising avenue for reducing post-stroke disability and improving the outcomes of long-term rehabilitation.By combining targeted drug delivery with the ability to modulate critical neuroprotective pathways,nanoparticles hold the potential to transform the treatment landscape for ischemic stroke.However,while preclinical data are highly encouraging,significant challenges remain in translating these advancements into clinical practice.Further research is needed to refine nanoparticle designs,optimize their safety profiles,and ensure their scalability for widespread application.Rigorous clinical trials are essential to validate their efficacy,assess long-term biocompatibility,and address potential off-target effects.The integration of interdisciplinary approaches,combining insights from nanotechnology,neuroscience,and pharmacology,will be critical if we are to overcome these challenges.Ultimately,nanoparticle-based therapies offer a foundation for innovative,precision-based treatments that could significantly improve outcomes for stroke patients,thus paving the way for a new era in stroke care and neurological rehabilitation.
文摘Background:This study focused on developing and optimizing a self-microemulsifying drug delivery system(SMEDDS)to improve Lafutidine’s solubility and bioavailability,thereby enhancing its effectiveness in treating gastric ulcers.Traditional formulations are less effective due to their limited water solubility and bioavailability.Methods:The study used solubility tests,pseudo-ternary phase diagrams,and central composite design(CCD)to optimize.The formulation was optimized by varying the oil concentration(10–40%)and surfactant/cosurfactant ratio(0.33–3.00),and then tested for droplet size,drug content,emulsification,phase stability,and in vitro dissolution.Results:The study found that the optimized formulation contained 14%Capmul PG 8NF oil,62%Labrasol surfactant,and 24%Tween 80 cosurfactant.This combination generated an average droplet size of 111.02 nm and improved drug release properties.Furthermore,the formulation was stable without phase separation,with a drug content of 88.2–99.8%.Conclusion:SMEDDS significantly improves lafutidine delivery by increasing solubility and absorption,thereby overcoming oral administration challenges.The system quickly formed small droplets in water and released the drug in 15 min.Enhancing lafutidine’s bioavailability may improve its efficacy in treating gastric ulcers,resulting in better patient outcomes and potentially lower dosing frequency.
文摘The development of cancer nanotherapeutics has attracted great interest in the recent decade. Cancer nanotherapeutics have overcome several limitations of conventional therapies, such as nonspecific biodistribution, poor water solubility, and limited bioavailability. Nanoparticles with tuned size and surface characteristics are the key components of nanotherapeutics, and are designed to passively or actively deliver anti-cancer drugs to tumor cells. We provide an overview of nanoparticle-based drug delivery methods and cancer therapies based on tumor-targeting delivery strategies that have been developed in recent years.
基金the financial support from the National Natural Science Foundation of China (Grant No.81373335)Liaoning Province Natural Science Foundation (Grant No.20170541025)
文摘RNA interfering(RNAi), mediated by small interfering RNAs and microRNAs, is currently one of the most promising tools of gene therapy. Small RNAs are capable of inducing specific post-transcriptional gene silencing, providing a potentially effective platform for the treatment of a wide array of diseases. However, similar to other nucleic acid-based drugs,the major hurdle of RNAi therapy is lack of efficient and non-immunogenic delivery vehicles. Currently, viruses, synthetic polymers, and lipid-based carriers are among the most widely studied vehicles for small RNA delivery. However, many drawbacks are reported to be associated with these delivery vehicles. There is a pressing need to replace them with more efficient and better-tolerated approaches. Exosomes secreted from the endocytic compartment of live cells, are a subtype of endogenous extracellular vesicles that transfer genetic and biochemical information among different cells, thus playing an important role in cellcell communication. Recently, accumulating attention has been focused on harnessing exosomes as nanaocarriers for small RNAs delivery. Due to their natural role in shuttling endogenous nucleic acid in our body, exosomes may exhibit higher delivery efficiency, lower immunogenicity, and better compatibility than existing foreign RNA carriers. Importantly,exosomes own intrinsic homing capacity that can guide small RNAs across natural membranous barriers. Moreover, such a capacity can be further improved by adding appropriate targeting moieties. In this manuscript, we briefly review the progress and challenges of RNAi therapy, and discuss the potential of exosomes' applications in small RNA delivery with focus on the most recent advances in exosome-based small RNA delivery for disease therapy.
