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
Every developing country has plans.Five-year frameworks,industrial master plans and poverty reduction strategies accumulate in ministerial offices year after year.Shelves fill.Expectations rise.Outcomes lag.The proble...Every developing country has plans.Five-year frameworks,industrial master plans and poverty reduction strategies accumulate in ministerial offices year after year.Shelves fill.Expectations rise.Outcomes lag.The problem is rarely vision.It is execution.China’s annual Two Sessions offer a window for the outside world to understand China’s governance system.Formally,they are the concurrent meetings of the National People’s Congress(NPC)and the National Committee of the Chinese People’s Political Consultative Conference.Substantively,they function as the central coordination mechanism of a developmental state that treats governance as an exercise in disciplined delivery.展开更多
Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsul...Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.展开更多
Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can si...Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.展开更多
Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availabilit...Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.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
1. Introduction Osteoarthritis(OA), traditionally viewed as a mechanical and degenerative condition, increasingly involves chronic,low-grade inflammation. Among implicated immune cells,activated macrophages are key dr...1. Introduction Osteoarthritis(OA), traditionally viewed as a mechanical and degenerative condition, increasingly involves chronic,low-grade inflammation. Among implicated immune cells,activated macrophages are key drivers of synovitis and cartilage degradation [1], spurring interest in therapies that selectively modulate macrophage activity within the joint while sparing other resident cells.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
Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to...Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.展开更多
Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability...Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.展开更多
Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techni...Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techniques,including X-ray diffraction,transmission electron microscopy(TEM),and X-ray photoelectron spectroscopy(XPS).XRD results reveal high crystallinity,with characteristic peaks corresponding to Nd_(2)Se_(3),while TEM analysis shows rod-shaped nanoparticles with an average size of~55 nm.The presence of neodymium and selenium in the+3 oxidation state was confirmed by XPS.Thermogravimetric analysis indicates that theβ-cyclodextrin-citrate coating accounts for approximately30%of the nanoparticle mass and remains stable up to 800℃.The optical properties of the nanoparticles were studied using UV-Vis-NIR spectroscopy,revealing broad absorption in the UV and NIR regions.Magnetic characterization shows soft ferromagnetic behavior,with a saturation magnetization value of0.20 emu/g.The nanoparticles were used for controlled release of 5-fluorouracil,exhibiting a pHsensitive release profile.Studies on MCF-7 cells demonstrate that 5-fluorouracil-loade d nanoparticles enhance cytotoxicity,reactive oxygen species generation,and apoptosis compared to bare nanoparticles.The IC_(50) value of(13.78±1.24)μg/mL indicates a significantly high cytotoxic activity of the drug-loaded nanoparticles against breast cancer cell lines.These findings suggest that the nanoparticles are a promising drug delivery system for enhanced cancer treatment,combining the controlled drug release with targeted cellular effects.展开更多
Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we devel...Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we developed hierarchical nanoparticles constructed through host-vip molecular recognition followed by electrostatic coassembly,yielding a formulation that unites high delivery efficiency with enhanced environmental compatibility.Relative to conventional wettable powders,these nanoparticles exhibited temperature-responsive release behavior and significantly enhanced foliar adhesion and deposition,increasing leaf retention by more than 241.7%.They also demonstrated strong resistance to rainfall wash-off and a markedly reduced propensity for groundwater leaching,with leaching losses decreased by approximately 18.6%.Greenhouse and field evaluations further confirmed their superior weed control under practical conditions,achieving control efficacies of up to 70.1%against Abutilon theophrasti and 52.9%against Setaria faberi,compared with 53.7%and 39.1%,respectively,for the commercial formulation at the same application rate.Extensive ecotoxicological assessments encompassing seed germination,zebrafish and earthworm assays,in vitro cellular tests,and in vivo rat studies consistently revealed an improved safety profile compared with commercial and technical formulations.Together,these results highlight hierarchical self-assembled nanoparticles as a promising platform for next-generation herbicide delivery that combines high target utilization with lower environmental impact and greater sustainability.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
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.
文摘Every developing country has plans.Five-year frameworks,industrial master plans and poverty reduction strategies accumulate in ministerial offices year after year.Shelves fill.Expectations rise.Outcomes lag.The problem is rarely vision.It is execution.China’s annual Two Sessions offer a window for the outside world to understand China’s governance system.Formally,they are the concurrent meetings of the National People’s Congress(NPC)and the National Committee of the Chinese People’s Political Consultative Conference.Substantively,they function as the central coordination mechanism of a developmental state that treats governance as an exercise in disciplined delivery.
文摘Food-grade biopolymers and nanotechnology have been increasingly used to revolutionize the delivery of bioactive compounds by enhancing stability,bioavailability,and controlled release.Within the scope of nanoencapsulation systems,this review explores food-derived polymers such as vicilin,zein,gluten,cruciferin,inulin,and others.These biopolymers are ideal since they encapsulate numerous functional compounds,such as vitamins,probiotics,essential oils,and polyphenols,because they are biocompatible,amphiphilic,and biodegradable.The specific physical and chemical properties of each polymer,extraction procedures,and nanoencapsulation techniques applied therein(e.g.,ionic gelation and spray drying)are described.The review highlights advanced targeting systems like pH-sensitive,magnetic delivery.Additional applications include those in synergistic nutraceutical systems,oral administration of vaccination,and intelligent food packaging.All these findings demonstrate that food polymers are increasingly more viable as functional nanocarriers by way of increasing bioactive delivery and the shifting requirements of personalized and health-based dietary regimes.
基金supported by the National Natural Science Foundation of China (No. 82373809 to Y.L., No. 825B2116 to J.L., No. 82373805 to N.Z., No. 82204295 to W.M)the Shandong Excellent Youth Fund and Provincial Natural Science Foundation (ZR2022YQ76 to Y.L., ZR2022QH224 to W.M.)。
文摘Tumors pose a serious threat to human life and health. In recent years, gene therapy against tumors has garnered considerable attention. Small interfering RNAs(siRNAs), an important class of nucleic acid drugs, can silence the m RNAs of tumor-associated genes with high specificity through RNA interference(RNAi), inhibiting tumor-related signaling pathways or protein expression and thereby exerting anti-tumor effects. However, antitumor siRNA drugs are currently in the clinical research stage, and none of these drugs have been approved for marketing, mainly because of the challenges in terms of safety,efficacy and targeted delivery. Nano-delivery systems can enhance siRNA stability and improve siRNA pharmacokinetics and biodistribution, while increasing their uptake by target cells to achieve precise delivery and controlled release, thereby serving as a promising solution to overcome the challenges of siRNA drug application. This review summarizes the existing research on the nano-delivery systems currently available to help siRNAs achieve organ-targeted delivery and enhance the anti-tumor efficacy of siRNAs, discussing the characteristics of siRNA action and the unique advantages of different types of nanodelivery systems. The aim was to provide novel ideas for the design and optimization of siRNA-based drug delivery and the development of novel anti-tumor formulations to promote the clinical translation and application of siRNA drugs.
文摘Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.
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supported by the National Natural Science Foundation of China (82372125 and 32471403)the Zhejiang Provincial Natural Science Foundation (LHDMY23H310002)Health Innovation Talents Program (Longfa Kou) from Health Commission of Zhejiang Province。
文摘1. Introduction Osteoarthritis(OA), traditionally viewed as a mechanical and degenerative condition, increasingly involves chronic,low-grade inflammation. Among implicated immune cells,activated macrophages are key drivers of synovitis and cartilage degradation [1], spurring interest in therapies that selectively modulate macrophage activity within the joint while sparing other resident cells.
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 National Natural Science Foundation of China (U22A20383)Natural Science Foundation of Zhejiang Province (LY24H300001)+2 种基金Fundamental Research Funds for the Central Universities (226-2022-00125)Zhejiang Province Postdoctoral Research Excellence Funding Project (ZJ2023151)Pharmacy 80 Basic Research Funding in College of Pharmaceutical Sciences, Zhejiang University Education Foundation。
文摘Asthma, one of the most prevalent chronic inflammatory diseases, remains challenging to manage effectively. Current therapies commonly alleviate symptoms through broad immunosuppression and bronchodilation but fail to target disease-specific molecular pathways. Genetic intervention using small interfering RNA(siRNA) has emerged as a promising strategy for asthma therapy. However, its success is largely hindered by the lack of an efficient delivery approach targeting airway epithelial cells(AECs). Here, we developed a novel inhalable siRNA delivery system based on artificially prepared nanovesicles through designed extrusion processes of mesenchymal stem cells. To enable an effective inhalation delivery of siRNA via nanovesicles, various parameters, including extrusion cycles,membrane pore sizes, and centrifugal forces were examined through orthogonal testing.Results revealed that the artificially prepared nanovesicles demonstrated remarkable capability to deliver thymic stromal lymphopoietin-targeted siRNA into AECs and substantially suppressed the inflammatory pathways and goblet cell hyperplasia, and eventually achieved a significant inhibition of asthma symptoms in ovalbumin-induced asthma models. Thus, the present study provides a novel nebulized nanovesicle-based carrier for effective delivery of siRNA through local inhalation, offering a promising therapeutic delivery platform for asthma and potentially other respiratory diseases.
基金supported by the National Natural Science Foundation of China(82373277).
文摘Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.
文摘Neodymium selenide nanoparticles were synthesized and surface-modified usingβ-cyclodextrin-citrate to control agglomeration and achieve the desired particle size.The nanoparticles were characterized by various techniques,including X-ray diffraction,transmission electron microscopy(TEM),and X-ray photoelectron spectroscopy(XPS).XRD results reveal high crystallinity,with characteristic peaks corresponding to Nd_(2)Se_(3),while TEM analysis shows rod-shaped nanoparticles with an average size of~55 nm.The presence of neodymium and selenium in the+3 oxidation state was confirmed by XPS.Thermogravimetric analysis indicates that theβ-cyclodextrin-citrate coating accounts for approximately30%of the nanoparticle mass and remains stable up to 800℃.The optical properties of the nanoparticles were studied using UV-Vis-NIR spectroscopy,revealing broad absorption in the UV and NIR regions.Magnetic characterization shows soft ferromagnetic behavior,with a saturation magnetization value of0.20 emu/g.The nanoparticles were used for controlled release of 5-fluorouracil,exhibiting a pHsensitive release profile.Studies on MCF-7 cells demonstrate that 5-fluorouracil-loade d nanoparticles enhance cytotoxicity,reactive oxygen species generation,and apoptosis compared to bare nanoparticles.The IC_(50) value of(13.78±1.24)μg/mL indicates a significantly high cytotoxic activity of the drug-loaded nanoparticles against breast cancer cell lines.These findings suggest that the nanoparticles are a promising drug delivery system for enhanced cancer treatment,combining the controlled drug release with targeted cellular effects.
基金supported by the University Synergy Innovation Program of Anhui Province(GXXT-2021-059)the National Key Research and Development Program of China(2023YFD1702102)the Major Natural Science Research Project of Anhui Universities(2023AH040143).
文摘Herbicides are indispensable for safeguarding global crop production,yet their effectiveness is often undermined by extensive environmental losses during application.Using herbicide Diuron as a model compound,we developed hierarchical nanoparticles constructed through host-vip molecular recognition followed by electrostatic coassembly,yielding a formulation that unites high delivery efficiency with enhanced environmental compatibility.Relative to conventional wettable powders,these nanoparticles exhibited temperature-responsive release behavior and significantly enhanced foliar adhesion and deposition,increasing leaf retention by more than 241.7%.They also demonstrated strong resistance to rainfall wash-off and a markedly reduced propensity for groundwater leaching,with leaching losses decreased by approximately 18.6%.Greenhouse and field evaluations further confirmed their superior weed control under practical conditions,achieving control efficacies of up to 70.1%against Abutilon theophrasti and 52.9%against Setaria faberi,compared with 53.7%and 39.1%,respectively,for the commercial formulation at the same application rate.Extensive ecotoxicological assessments encompassing seed germination,zebrafish and earthworm assays,in vitro cellular tests,and in vivo rat studies consistently revealed an improved safety profile compared with commercial and technical formulations.Together,these results highlight hierarchical self-assembled nanoparticles as a promising platform for next-generation herbicide delivery that combines high target utilization with lower environmental impact and greater sustainability.
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.
