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
A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an or...A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.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
Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,...Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.展开更多
In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of curr...In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.展开更多
In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the e...In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.展开更多
Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments re...Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.展开更多
Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced ...Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.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
Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused...Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Mat...Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Maternity and Child Healthcare Hospital from July 2023 to July 2024.The participants were divided into a control group and an observation group,with 50 cases in each.The division was based on the indications for prior cesarean section,cervical maturity,postpartum complications,and thickness of the cesarean scar.The control group underwent cesarean delivery,while the observation group experienced vaginal delivery.The two groups were compared in terms of intrapartum blood loss,postpartum blood loss within 2 hours,length of hospital stay,Apgar scores at 1-minute post-birth,and incidences of neonatal fever and jaundice.Results:The observation group had significantly lower intrapartum blood loss,postpartum blood loss within 2 hours,and shorter hospital stays compared to the control group(P<0.05).Additionally,the Apgar scores at 1 minute post-birth were significantly higher in the observation group(P<0.05).The incidence of neonatal fever and jaundice was significantly lower in the observation group(P<0.05).These differences were statistically significant.Conclusion:Vaginal delivery has high clinical value for women with repeat pregnancies involving uterine scars.It reduces maternal intrapartum and postpartum blood loss,shortens hospital stays,improves neonatal Apgar scores,and decreases the incidences of neonatal fever and jaundice.This method is worthy of clinical application and promotion.展开更多
In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited re...In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited retinal diseases,hemophilia,and Duchenne muscular dystrophy,among others.However,AAV-based therapies still face challenges,including immune responses and side effects,due to high viral doses.To address these challenges,various strategies have been developed,such as creating new viral capsids,optimizing gene expression regulation,and improving delivery methods.Localized delivery is a promising direction,utilizing the tissue tropism of AAVs to reduce systemic side effects and lower the required viral dose,thus improving targeting and efficiency,especially for organs that are difficult to treat with conventional methods.These innovations have opened new pathways for the clinical application of AAVs.This review aims to provide a comprehensive summary of the various applications of AAVs,offer valuable insights for future research directions,and holds significant importance for researchers and clinicians in the field.As AAV therapy continues to evolve,this article emphasizes its transformative potential in treating genetic diseases,indicating the central role of AAV in the future of gene therapy.展开更多
Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or force...Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.展开更多
With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the ve...With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the vehicle and its onboard UAVs are utilized efficiently. Vehicles not only provide delivery services to customers but also function as mobile ware-houses and launch/recovery platforms for UAVs. This paper addresses the vehicle routing problem with UAVs considering time window and UAV multi-delivery (VRPU-TW&MD). A mixed integer linear programming (MILP) model is developed to mini-mize delivery costs while incorporating constraints related to UAV energy consumption. Subsequently, a micro-evolution aug-mented large neighborhood search (MEALNS) algorithm incor-porating adaptive large neighborhood search (ALNS) and micro-evolution mechanism is proposed. Numerical experiments demonstrate the effectiveness of both the model and algorithm in solving the VRPU-TW&MD. The impact of key parameters on delivery performance is explored by sensitivity analysis.展开更多
Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent bioc...Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.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
Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphili...Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphilic NPs generally involve several steps,especially an additional step for surface modification,greatly hindering their largescale production and widespread applications.Here,a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property.The amphiphilic dimer NPs,which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid)(PLA)bulb with PLA-poly(ethylene glycol)(PEG)on the bulb surface,are prepared in a single step by controlled co-precipitation and self-assembly.Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology,thus showing good performances in controlling the interfacial curvature and emulsion type.In addition,temperatureresponsive PLA-poly(N-isopropyl acrylamide)(PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response.The applications of PLA-PEG-folic acid(FA)/shellac dimer NPs for drug delivery have also been demonstrated,which show a very good performance.The strategy of preparing the dimer NPs is green,scalable,facile and versatile,which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications.展开更多
The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers...The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.展开更多
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.
文摘A recently published study(Xin et al.,Prog Biochem Biophys,2026,53(2):431-441.DOI:10.3724/j.pibb.2025.0508)addresses the therapeutic challenges of pancreatic ductal adenocarcinoma(PDAC)by innovatively developing an orally administered nanogene delivery system.Designed to achieve in situ,efficient delivery of chimeric antigen receptor(CAR)genes to tumor sites,this approach offers a novel strategy for CAR-macrophage(CAR-M)based immunotherapy.Its key highlights are as follows.
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financial support from the Noncommunicable Chronic Diseases-National Science and Technology Major Project (Nos.2024ZD0522800,2024ZD0522803)the National Natural Science Foundation of China (Nos.U21A20417,31930067,31800797)+2 种基金the Natural Science Foundation of Sichuan Province (No.2024NSFSC0046)the Sichuan Science and Technology Program (No.2022YFS0333)the 1·3·5 Project for Disciplines of Excellence,West China Hospital,Sichuan University (No.ZYGD24003)。
文摘Malignant pleural effusion(MPE) is a serious disease caused by malignant tumors with high morbidity and mortality.Chemotherapy,immunotherapy,and antiangiogenic therapy are common treatments for MPE at present.However,traditional chemotherapeutic drugs have many side effects and can easily lead to drug resistance in patients.The complex tumor microenvironment(TME) of MPE directly reduces the antitumor efficacy of immunotherapy.Fortunately,drug delivery systems(DDSs) based on biomaterials have the ability to overcome some of the drawbacks of conventional treatments by improving drug stability,increasing the accuracy of tumor cell targeting,reducing toxic side effects,and remodeling TME,ultimately improving drug efficacy.Therefore,the purpose of this review is to provide an overview and discussion of the latest progress in biomaterial-based DDSs for the treatment of MPE.We discuss the application of biomaterials in the treatment of MPE from multiple perspectives,including chemotherapy,immunotherapy,combination therapy,and pleurodesis,where microspheres,cell membrane-derived microparticles(MPs),micelles,nanoparticles,and liposomes,are involved.The application of these biomaterials has been proven to have great potential in the treatment of MPE,providing a new idea for follow-up research.
基金funded by the National Natural Science Foundation of China (No.NSFC82400096)Science and Technology Department of Sichuan Province (No.2025ZNSFSC1538)Xihua University Internal Talent Introduction Project with Scientific Research Funding (No.ZX20250087)。
文摘In recent years,different drugs therapies for treatment pulmonary fibrosis(PF) have gained much attention due to development of drug delivery technology and urgent clinical needs.PF treatment existed a variety of currently clinical problem but PF could be treated with different drugs potentially though drug delivery technology.This review systematically expounds its basic theory,various drug delivery technologies,and future development directions.In the introduction,the relationship between the pathological mechanism of PF and drug delivery,the basic principles of the drug delivery system and the biological barriers faced by pulmonary drug delivery are analyzed.This review details delivery of small molecule drug,macromolecular drug and cells,including chemical synthesis and natural small molecule drug delivery,as well as RNA and cell-based delivery.Finally,the challenges and perspectives of these drugs to treat PF delivery technologies are discussed and key aspects in the development of PF drugs are considered.We hoped that this review can provide comprehensive and in-depth theoretical reference and technical support for the drug treatment of PF.
基金funded by the Fundamental Research Funds for the Central Universities (No.2242022R42012)。
文摘In recent years,development of strategies to treat central nervous system(CNS) diseases has attracted extensive attention.A major obstacle in this field is the blood-brain barrier(BBB),which significantly limits the efficient delivery of therapeutic agents to the brain and hinders the treatment of CNS diseases.Overcoming the restrictive nature of the BBB has thus emerged as a key objective in CNS drug development.Nanomaterials have garnered growing interest due to their unique physicochemical properties and potential to traverse the BBB,enabling targeted drug delivery to brain tissue and improving therapeutic efficacy.In this review,we present current insights into the structure and function of the BBB and highlight a range of nanomaterial-based strategies for BBB penetration,including receptor-mediated transport(RMT),adsorptive-mediated transcytosis,reversible BBB disruption,and intranasal administration.Finally,we summarize recent advances in enhancing BBB permeability for CNS therapeutics and discuss persisting challenges,offering perspectives for future research in this field.
基金the National Natural Science Foundation of China(No.21921003 for Z.T.L.and 22201293 for S.B.Y.)Shanghai Sailing Program(No.22YF1458300 for S.B.Y.)for financial support。
文摘Two supramolecular organic frameworks(SOFs)have been constructed from the co-assembly of biimidazolium-derived octacationic components and cucurbit[8]uril in water.Dynamic light scattering and ^(1)H NMR experiments reveal that both SOFs can undergo reversible assembly and disassembly at room temperature.One of the SOFs displays unprecedently high maximum tolerated dose of 120 mg/kg with mice,which improves by 40%compared with the highest value of the reported SOFs.In vitro and in vivo tests show that the SOF can adsorb doxorubicin and overcome the resistance of multidrugresistant MDR A549/ADR tumor cells to realize intracellular delivery,leading to enhanced antitumor efficacy.Moreover,it can also completely inhibit the posttreatment phototoxicity of photofrin and fully neutralize the anticoagulation of both unfractionated heparin and low molecular weight heparins through efficient inclusion and elimination or sequestration mechanism.As the first examples that undergo roomtemperature reversible assembly and disassembly,the new SOFs in principle allow for quantitative analysis of the molecular components in the body that is prerequisite for preclinical evaluation in the future.
基金funded by the Deanship of Scientific Research at King Abdulaziz University,Jeddah,under Grant No.G:534-140-1443.
文摘Objective:To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system(PIC-SNEDDS)on wound healing in diabetic rats and its mechanisms of wound healing action.Methods:Diabetes was induced in rats using streptozotocin,after which full-thickness excisional wounds were created.Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS,which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application.Wound healing activity was assessed through measurements of wound contraction,oxidative stress biomarkers,and collagen content,along with histological and immunohistochemical evaluation of inflammatory,angiogenic,and remodeling markers.Results:PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration,granulation tissue formation,epidermal proliferation,and keratinization.The formulation also reduced the expression of pro-inflammatory markers(interleukin-6,nuclear factor-kappa B,and tumor necrosis factor-α)while increasingα-smooth muscle actin,transforming growth factor-β1,vascular endothelial growth factor-A,and hydroxyproline levels.Additionally,it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity,along with upregulation of COL1A1 mRNA expression.Conclusions:PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory,antioxidant,pro-collagen,and angiogenic properties.
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.
基金supported by the following grants:National Natural Science Foundation of China(Grant Nos.92354305 and 32271428),National Key R&D Program of China(Grant No.2022YFC3401100)Young Talent Program of Hubei Provincial Health Commission(WJ2025Q037)+1 种基金Interdisciplinary Research Program of HUST(Grant No.2023JCY5045)Director Fund of WNLO.
文摘Fluorescent probes,with their superior optical properties and labeling versatility,have greatly advanced the visualization of intracellular molecules and subcellular structures.However,poor cytoplasmic delivery,caused by charge,size,or targeting groups,limits the effective use of many fluorescent probes in live cells.Recently,cell-penetrating peptides(CPPs)have emerged as efficient carriers,offering great potential for the cytoplasmic delivery of fluorescent probes in live cells.This review provides a comprehensive overview of CPPs as vehicles for probe delivery,outlining advances in their development,conjugation chemistries,and intracellular delivery mechanisms.Recent applications in live-cell imaging are highlighted and organized according to major CPP modification strategies,including sequence engineering,cyclization,hybrid design and enhancement by chemical reagents.Finally,the challenges that remain and the future outlook of this rapidly evolvingfield are discussed.
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
文摘Objective:To investigate the delivery modes of women with repeat pregnancies involving uterine scars and their effects on both mothers and neonates.Methods:A study was conducted on 100 patients treated at Shenzhen Maternity and Child Healthcare Hospital from July 2023 to July 2024.The participants were divided into a control group and an observation group,with 50 cases in each.The division was based on the indications for prior cesarean section,cervical maturity,postpartum complications,and thickness of the cesarean scar.The control group underwent cesarean delivery,while the observation group experienced vaginal delivery.The two groups were compared in terms of intrapartum blood loss,postpartum blood loss within 2 hours,length of hospital stay,Apgar scores at 1-minute post-birth,and incidences of neonatal fever and jaundice.Results:The observation group had significantly lower intrapartum blood loss,postpartum blood loss within 2 hours,and shorter hospital stays compared to the control group(P<0.05).Additionally,the Apgar scores at 1 minute post-birth were significantly higher in the observation group(P<0.05).The incidence of neonatal fever and jaundice was significantly lower in the observation group(P<0.05).These differences were statistically significant.Conclusion:Vaginal delivery has high clinical value for women with repeat pregnancies involving uterine scars.It reduces maternal intrapartum and postpartum blood loss,shortens hospital stays,improves neonatal Apgar scores,and decreases the incidences of neonatal fever and jaundice.This method is worthy of clinical application and promotion.
基金supported by the Guiding Funds of Central Government for Supporting the Development of the Local Science and Technology(2024BSB012)National Natural Science Foundation of China(No.81772833).
文摘In recent years,adeno-associated viruses(AAVs)have emerged as leading vectors in gene therapy,with several FDA-approved treatments and ongoing clinical trials demonstrating their effectiveness in treating inherited retinal diseases,hemophilia,and Duchenne muscular dystrophy,among others.However,AAV-based therapies still face challenges,including immune responses and side effects,due to high viral doses.To address these challenges,various strategies have been developed,such as creating new viral capsids,optimizing gene expression regulation,and improving delivery methods.Localized delivery is a promising direction,utilizing the tissue tropism of AAVs to reduce systemic side effects and lower the required viral dose,thus improving targeting and efficiency,especially for organs that are difficult to treat with conventional methods.These innovations have opened new pathways for the clinical application of AAVs.This review aims to provide a comprehensive summary of the various applications of AAVs,offer valuable insights for future research directions,and holds significant importance for researchers and clinicians in the field.As AAV therapy continues to evolve,this article emphasizes its transformative potential in treating genetic diseases,indicating the central role of AAV in the future of gene therapy.
文摘Background: The maternal and neonatal morbidity caused by prolonged labour, maternal exhaustion and other factors push clinicians to speed up the delivery process by employing equipment such as vacuum suction or forceps to save the newborn. The purpose of this study was to determine the prevalence of vacuum-assisted vaginal delivery (VAVD) and its associated short-term maternal and neonatal outcomes at Ndola Teaching Hospital. Methods: A retrospective cross-sectional descriptive study through the analysis of routine data for women with singleton-term pregnancies who delivered by vacuum compared with spontaneous vaginal delivery was done at a tertiary hospital for the years 2020 and 2021. Chi-square and Logistic regression were used to investigate factors of vacuum delivery and to adjust for potential confounders. Results: Results showed that VAVD was mostly performed in women who had delayed second stage of labour (25.4%), maternal exhaustion (16.0%), foetal distress in the second stage of labour (12.3%). The overall VAVD prevalence was 3.7% (581/15591). Logistic regression showed that multiparous women were noted to be 87.5% (aOR 0.125;95% CI 0.025 - 0.629;p = 0.012) less likely to undergo VAVD compared to nulliparous women. Registrars were almost 6 times (aOR 5.650;95% CI 1.458 - 22.222, p = 0.012) more likely to conduct VAVD compared to midwives. Episiotomy was 3 times (aOR 3.390;95% CI 1.185 - 9.524;p Conclusion: The findings indicate the underutilisation of VAVD at NTH based on the low prevalence of 3.7%. VAVD outcomes were affected by multiparity, skill level and Episiotomy procedure, in addition, VAVD influenced admission to the NICU. Hence, there is a need to increase skills in VAVD among first-line healthcare workers such as midwives and intern doctors.
基金supported by the Fundamental Research Funds for the Central Universities(2024JBZX038)the National Natural Science Foundation of China(62076023).
文摘With the rapid development of low-altitude economy and unmanned aerial vehicles (UAVs) deployment technology, aerial-ground collaborative delivery (AGCD) is emerging as a novel mode of last-mile delivery, where the vehicle and its onboard UAVs are utilized efficiently. Vehicles not only provide delivery services to customers but also function as mobile ware-houses and launch/recovery platforms for UAVs. This paper addresses the vehicle routing problem with UAVs considering time window and UAV multi-delivery (VRPU-TW&MD). A mixed integer linear programming (MILP) model is developed to mini-mize delivery costs while incorporating constraints related to UAV energy consumption. Subsequently, a micro-evolution aug-mented large neighborhood search (MEALNS) algorithm incor-porating adaptive large neighborhood search (ALNS) and micro-evolution mechanism is proposed. Numerical experiments demonstrate the effectiveness of both the model and algorithm in solving the VRPU-TW&MD. The impact of key parameters on delivery performance is explored by sensitivity analysis.
基金supported by the grants from University of Macao,China,Nos.MYRG2022-00221-ICMS(to YZ)and MYRG-CRG2022-00011-ICMS(to RW)the Natural Science Foundation of Guangdong Province,No.2023A1515010034(to YZ)。
文摘Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on society.Extracellular vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic stroke.However,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery efficiency.By utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly improved.Furthermore,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic stroke.Small extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke therapy.In this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification methodologies.Given the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment process.Moreover,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
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.
基金supported by National Natural Science Foundation of China(No.22278352)National Key Research and Development Program of China(No.2021YFC3001100)+3 种基金Longyan City Science and Technology Plan Project(No.2020LYF17043)Longyan City Science and Technology Plan Project(No.2020LYF17042)ARC Discovery Project(No.DP200101238)and NHMRC Investigator Grant(No.APP2008698)supported by the Harvard Materials Research Science and Engineering Center(No.DMR2011754)。
文摘Biocompatible amphiphilic nanoparticles(NPs)with tunable particle morphology and surface property are important for their applications as functional materials.However,previously developed methods to prepare amphiphilic NPs generally involve several steps,especially an additional step for surface modification,greatly hindering their largescale production and widespread applications.Here,a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property.The amphiphilic dimer NPs,which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid)(PLA)bulb with PLA-poly(ethylene glycol)(PEG)on the bulb surface,are prepared in a single step by controlled co-precipitation and self-assembly.Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology,thus showing good performances in controlling the interfacial curvature and emulsion type.In addition,temperatureresponsive PLA-poly(N-isopropyl acrylamide)(PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response.The applications of PLA-PEG-folic acid(FA)/shellac dimer NPs for drug delivery have also been demonstrated,which show a very good performance.The strategy of preparing the dimer NPs is green,scalable,facile and versatile,which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications.
基金supported by National Natural Science Foundation of China(82104082)Natural Science Foundation of Qinghai Province(2024-ZJ-911).
文摘The recent commercialization of gene products has sparked significant interest in gene therapy,necessitating efficient and precise gene delivery via various vectors.Currently,viral vectors and lipid-based nanocarriers are the predominant choices and have been extensively investigated and reviewed.Beyond these vectors,polymeric nanocarriers also hold the promise in therapeutic gene delivery owing to their versatile functionalities,such as improving the stability,cellar uptake and endosomal escape of nucleic acid drugs,along with precise delivery to targeted tissues.This review presents a brief overview of the status quo of the emerging polymeric nanocarriers for therapeutic gene delivery,focusing on key cationic polymers,nanocarrier types,and preparation methods.It also highlights targeted diseases,strategies to improve delivery efficiency,and potential future directions in this research area.The review is hoped to inspire the development,optimization,and clinical translation of highly efficient polymeric nanocarriers for therapeutic gene delivery.
