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
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
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
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
Targeted drug delivery platforms are designed to enable spatiotemporal precision in transporting therapeutic agents to disease-specific sites,thereby optimizing therapeutic efficacy and mitigating off-target adverse e...Targeted drug delivery platforms are designed to enable spatiotemporal precision in transporting therapeutic agents to disease-specific sites,thereby optimizing therapeutic efficacy and mitigating off-target adverse effects.Despite their clinical promise,these platforms remain hindered by substantial translational barriers.Macrophages,with inherent biocompatibility and intrinsic tropism toward inflamed/diseased tissues,are critically involved in diverse pathological processes.Macrophage-based drug delivery systems(MDDSs)have emerged as promising platforms engineered via therapeutic cargo loading onto intact cells,cell-membrane coatings,extracellular vesicles(EVs),or hitchhiking mechanisms.This review delineates existing MDDS platforms,critically analyzing their respective merits and constraints.We further elucidate therapeutic mechanisms and clinical implementations of MDDSs for cancer,atherosclerosis(AS),and central nervous system(CNS)disorders,while establishing a systematic taxonomy of their biomedical applications.Specifically,we highlight the transformative potential of gene-editing technologies(exemplified by chimeric antigen receptor macrophage(CAR-M)therapy and antigen-independent strategies)in innovating next-generation MDDS architectures.We summarize state-of-the-art developments,persisting translational hurdles,and optimization roadmaps for MDDSs,providing a conceptual framework to guide their translational advancement.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
Photothermal therapy(PTT),characterized by its minimally invasive nature and highly selective tumorkilling ability,holds great potential for tumor therapy.Due to the outstanding photothermal performance and tumor targ...Photothermal therapy(PTT),characterized by its minimally invasive nature and highly selective tumorkilling ability,holds great potential for tumor therapy.Due to the outstanding photothermal performance and tumor targeting ability,nanomaterial-based photothermal agents(nano-PTAs)have further expanded the therapeutic horizons of PTT.However,the dense and complicated network of the tumor extracellular matrix(ECM)severely restricts the penetration of nano-PTAs into deep tumor tissues.Since elevated temperatures are only generated in the vicinity of nano-PTAs upon laser irradiation,the uneven distribution of these agents leads to incomplete tumor coverage across the tumor.Consequently,overcoming ECM barriers and enhancing tumor permeability are critical for the success of tumor PTT.To address this challenge,researchers have explored strategies that combine tumor ECM regulation with PTT to facilitate the deep diffusion of nano-PTAs.This review summarizes the latest advancements in designing nanoPTAs with ECM-remodeling capabilities,aiming to enable their uniform penetration throughout tumors.Additionally,we discuss the remaining obstacles and challenges in elucidating the mechanisms of ECM manipulation and understanding the interactions between nano-PTAs and ECM components during the penetration process.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
Lignin,the most abundant natural aromatic polymer globally,has garnered considerable interest due to its rich and diverse active functional groups and its antioxidant,antimicrobial,and adhesive properties.Recent resea...Lignin,the most abundant natural aromatic polymer globally,has garnered considerable interest due to its rich and diverse active functional groups and its antioxidant,antimicrobial,and adhesive properties.Recent research has significantly improved the performance of lignin-based hydrogels,suggesting their substantial potential in fields such as biomedicine,environmental science,and agriculture.This paper reviews the process of lignin extraction,systematically introduces synthesis strategies for preparing lignin-based hydrogels,and discusses the current state of research on these hydrogels in biomedical and environmental protection fields.It concludes by identifying the existing challenges in lignin hydrogel research and envisioning future prospects and development trends.展开更多
As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable ef...As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable efficacy in a range of applications,including epidemic vaccine,cancer vaccine,protein replacement therapy,cytokine therapy,cell therapy and gene editing.Due to the inherent instability of mRNA,the rational design of mRNA structure is the prerequisite for therapeutic utility while effective delivery systems are also essential for in vivo applications.This review focuses on the optimization of mRNA structure and highlights key delivery strategies.It also provides a comprehensive overview of the major applications of mRNA-based strategies.In addition,it highlights the persistent challenges in m RNA therapeutics,particularly in terms of stability,immunogenicity,delivery efficiency and safety.By examining recent advances in mRNA design,delivery and application,this review aims to support ongoing research and development in the field of mRNA-based therapeutics.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
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
The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierar...The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.展开更多
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.
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supported by the National Key R&D Program of China(Grant No.:2024YFA1210100)the Natural Science Foundation of China(Grant No.:82273877)+1 种基金the Natural Science Foundation of Sichuan Province,China(Grant No.:2023NSFSC1680)the Science and Technology Project of Chengdu City,China(Grant No.:2022-YF05-01398-SN).
文摘Targeted drug delivery platforms are designed to enable spatiotemporal precision in transporting therapeutic agents to disease-specific sites,thereby optimizing therapeutic efficacy and mitigating off-target adverse effects.Despite their clinical promise,these platforms remain hindered by substantial translational barriers.Macrophages,with inherent biocompatibility and intrinsic tropism toward inflamed/diseased tissues,are critically involved in diverse pathological processes.Macrophage-based drug delivery systems(MDDSs)have emerged as promising platforms engineered via therapeutic cargo loading onto intact cells,cell-membrane coatings,extracellular vesicles(EVs),or hitchhiking mechanisms.This review delineates existing MDDS platforms,critically analyzing their respective merits and constraints.We further elucidate therapeutic mechanisms and clinical implementations of MDDSs for cancer,atherosclerosis(AS),and central nervous system(CNS)disorders,while establishing a systematic taxonomy of their biomedical applications.Specifically,we highlight the transformative potential of gene-editing technologies(exemplified by chimeric antigen receptor macrophage(CAR-M)therapy and antigen-independent strategies)in innovating next-generation MDDS architectures.We summarize state-of-the-art developments,persisting translational hurdles,and optimization roadmaps for MDDSs,providing a conceptual framework to guide their translational advancement.
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financially supported by the National Natural Science Foundation of China(Nos.22074072,22274083,32171362)the Natural Science Foundation of Shandong Province(Nos.ZR2022LZY022,ZR2023LZY005,ZR2022YQ73,ZR2021MH087,ZR2024MH070)+1 种基金Special Funds of the Taishan Scholar Program of Shandong Province(No.tsqn202306168)Traditional Chinese Medicine Science and Technology Project of Shandong Province(No.M-2023124)。
文摘Photothermal therapy(PTT),characterized by its minimally invasive nature and highly selective tumorkilling ability,holds great potential for tumor therapy.Due to the outstanding photothermal performance and tumor targeting ability,nanomaterial-based photothermal agents(nano-PTAs)have further expanded the therapeutic horizons of PTT.However,the dense and complicated network of the tumor extracellular matrix(ECM)severely restricts the penetration of nano-PTAs into deep tumor tissues.Since elevated temperatures are only generated in the vicinity of nano-PTAs upon laser irradiation,the uneven distribution of these agents leads to incomplete tumor coverage across the tumor.Consequently,overcoming ECM barriers and enhancing tumor permeability are critical for the success of tumor PTT.To address this challenge,researchers have explored strategies that combine tumor ECM regulation with PTT to facilitate the deep diffusion of nano-PTAs.This review summarizes the latest advancements in designing nanoPTAs with ECM-remodeling capabilities,aiming to enable their uniform penetration throughout tumors.Additionally,we discuss the remaining obstacles and challenges in elucidating the mechanisms of ECM manipulation and understanding the interactions between nano-PTAs and ECM components during the penetration process.
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].
基金supported by the National Natural Science Foundation of China(21706052,22278114)Natural Science Foundation of Henan Province(242300421575).
文摘Lignin,the most abundant natural aromatic polymer globally,has garnered considerable interest due to its rich and diverse active functional groups and its antioxidant,antimicrobial,and adhesive properties.Recent research has significantly improved the performance of lignin-based hydrogels,suggesting their substantial potential in fields such as biomedicine,environmental science,and agriculture.This paper reviews the process of lignin extraction,systematically introduces synthesis strategies for preparing lignin-based hydrogels,and discusses the current state of research on these hydrogels in biomedical and environmental protection fields.It concludes by identifying the existing challenges in lignin hydrogel research and envisioning future prospects and development trends.
基金supported by the National Key Research and Development Program of China(No.2023YFA0915400)the National Natural Science Foundation of China(No.22277072,22407099 and 32401161)+3 种基金Shanghai Oriental Talents(QNWS2024055)Shanghai Municipal Science and Technology Commission(No.24ZR1462700)the Science and Technology Development Fund of Pudong Health Bureau of Shanghai(No.PKJ2024-Y40)“Clinic Plus”Outstanding Project(No.2021ZYB009 and No.2021ZYB003)from Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine,and Innovative research team of high-level local universities in Shanghai。
文摘As the central template for protein expression,messenger ribonucleic acid(mRNA)holds immense potential for novel therapeutic strategies.Over the past few decades,mRNA-based therapeutics have demonstrated remarkable efficacy in a range of applications,including epidemic vaccine,cancer vaccine,protein replacement therapy,cytokine therapy,cell therapy and gene editing.Due to the inherent instability of mRNA,the rational design of mRNA structure is the prerequisite for therapeutic utility while effective delivery systems are also essential for in vivo applications.This review focuses on the optimization of mRNA structure and highlights key delivery strategies.It also provides a comprehensive overview of the major applications of mRNA-based strategies.In addition,it highlights the persistent challenges in m RNA therapeutics,particularly in terms of stability,immunogenicity,delivery efficiency and safety.By examining recent advances in mRNA design,delivery and application,this review aims to support ongoing research and development in the field of mRNA-based therapeutics.
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.
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financially supported by National Natural Science Foundation of China (No.3240117,X.S)Sichuan Science and Technology Program (No.2024YFFK0345,Z.X)+3 种基金Natural Science Foundation of Chongqing (No.CSTB2024NSCQ-MSX0046,F.R)Startup Fund of Chongqing Normal University (No.23XLB036,F.R)National College Student Innovation and Entrepreneurship Program of Southwest University (No.202410635109,Y.Z)Guangdong High-level Hospital Construction Fund。
文摘The development of highly effective therapeutics is a priority in addressing the escalating threat that cancer poses to human health.Cyclodextrins(CDs) with exceptional biocompatibility and devisable structural hierarchy are emerging as versatile building blocks for engineered drug delivery systems,showing a promising prospect in cancer therapy.CDs enable precise synthesis of functionalized polymers with tailored architectures,endowing their excellent stability and large surface area to prolong drug circulation,enhance solubility,and increase targeting efficiency.Recently,CD-based nanotherapeutics has shown transformative potential in chemotherapy,phototherapy,immunotherapy,gene therapy and other codelivery systems of combination therapy.This review will introduce the types of CD-based nanotherapeutics,systematically summarize their design methods and anticancer application,and further discuss the prospects and challenges,providing a roadmap for advancing CD nanotechnology toward cancer therapeutics.
