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
Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing fac...Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.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
The treatment of tumors continues to be significantly challenging. The presence of multiple modalities, including surgery, radiation, chemotherapy and immunotherapy, the therapeutic outcomes remain limited and are oft...The treatment of tumors continues to be significantly challenging. The presence of multiple modalities, including surgery, radiation, chemotherapy and immunotherapy, the therapeutic outcomes remain limited and are often associated with adverse effects and inconsistent efficacy across cancer types. Recent studies have highlighted the potential of active components from traditional Chinese medicine(TCM) for their anti-cancer properties, which are attributable to multi-targeted mechanisms and broad pharmacological actions. Despite this potential, TCM-derived compounds are commonly limited by poor water solubility, low bioavailability, and suboptimal targeting. Currently, it is believed that advances in nanotechnology could address these limitations. Nanoparticles(NPs),which possess properties such as enhanced bioavailability, controlled release and precise targeting, have been used to improve the therapeutic efficacy of TCM components in cancer therapy. This review discusses the use of NPs for the delivery of active TCM compounds via organic-inorganic nanocarriers, highlighting innovative strategies that enhance the effectiveness of TCM-based anti-tumor components to provide insights into improving clinical outcomes while advancing the modernization and global application of TCM in oncology.展开更多
Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and ...Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.展开更多
In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a func...In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.展开更多
Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lackin...Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.展开更多
Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been som...Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.展开更多
In order to deliver and/or release anti-cancer therapeutics at the tumor sites, novel environment-responsive drug delivery systems are designed to specifically respond to tumor microenvironment （such as low pH and hy...In order to deliver and/or release anti-cancer therapeutics at the tumor sites, novel environment-responsive drug delivery systems are designed to specifically respond to tumor microenvironment （such as low pH and hypoxia）. Due to their extraordinary advantages, these environment-responsive drug delivery systems can improve antitumor efficacy, and most importantly, they can decrease toxicity associated with the anti-cancer therapeutics. This review highlights different mechanisms of environmentresponsive drug delivery systems and their applications for targeted cancer therapy.展开更多
Inflammatory bowel disease(IBD)is a chronic illness characterized by relapsing inflammation of the intestines.The disorder is stratified according to the severity and is marked by its two main phenotypical representat...Inflammatory bowel disease(IBD)is a chronic illness characterized by relapsing inflammation of the intestines.The disorder is stratified according to the severity and is marked by its two main phenotypical representations:Ulcerative colitis and Crohn’s disease.Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition,environmental factors such as bacterial agents,and dysregulated immune response.Treatment for IBD aims to reduce symptom extent and severity and halt disease progression.The mainstay drugs have been 5-aminosalicylates(5-ASAs),corticosteroids,and immunosuppressive agents.Parenteral,oral and rectal routes are the conventional methods of drug delivery,and among all,oral administration is most widely adopted.However,problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery.Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues.Enteric-coated microneedle pills,various nano-drug delivery techniques,prodrug systems,lipid-based vesicular systems,hybrid drug delivery systems,and biologic drug delivery systems constitute some of these novel methods.Microneedles are painless,they dislodge their content at the affected site,and their release can be prolonged.Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells,including GM immune cells and red blood cells as nanoparticle carriers,can be plausible delivery methods when evaluating biologic systems.Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site.Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage.Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems,while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too.Leukosomes are also considered as possible carrier systems,and results from mouse models have revealed that they control anti-and pro-inflammatory molecules.展开更多
Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industr...Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industrial production of these systems,and solution strategies for these challenges.Further,we analyze and discuss the frontier medical applications of cell membrane-camouflaged drug delivery systems in anti-inflammatory,anti-pathogenic microorganisms,and biological detoxification.This review takes a challenge-oriented perspective and seeks innovative strategies,provides a literature review of research into cell membrane-camouflaged drug delivery systems,and promotes the development of personalized clinical treatments.展开更多
Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therape...Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.展开更多
Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, th...Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.展开更多
Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical trea...Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.展开更多
Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective deli...Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.展开更多
The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of lif...The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.展开更多
In recent years, cancer has become the number two cause of death around the world, and scientists have exploited various treatment maps. Calixarenes, with diversified features, have been widely applied into drug deliv...In recent years, cancer has become the number two cause of death around the world, and scientists have exploited various treatment maps. Calixarenes, with diversified features, have been widely applied into drug delivery systems, which can respond to multi-stimuli and exhibit excellent performance. In this mini-review, we summarize the recent advances on controlled drug delivery systems based on calixarenes, in the form of inclusion complexes, amphiphilic self-assembly nanocarriers including micelles, hydrogels, vesicles and liposomes, and supramolecular nanovalves on mesoporous silica nanomaterials.展开更多
Polye-caprolactone）-b-poly（ethylene glycol）-b-poly（e-caprolactone）（PCL-b-PEG-b-PCL,PCEC） triblock copolymers have been widely investigated in last several decades.Here,by altering the weight ratio of monomers i...Polye-caprolactone）-b-poly（ethylene glycol）-b-poly（e-caprolactone）（PCL-b-PEG-b-PCL,PCEC） triblock copolymers have been widely investigated in last several decades.Here,by altering the weight ratio of monomers in ring-opening polymerization,a series of PCEC triblock copolymers with varying hydrophobicity were synthesized,which were characterized by FTIR,1 H NMR,GPC and DSC.When PCEC copolymers with different weight ratios of PCL/PEG were dispersed in different aqueous solutions,they could self-assemble and form two distinctive nanoparticular structures：micelles or polymersomes.We then chose paclitaxel（PTX） as the model drug and encapsulate PTX into PCEC polymeric micelles and polymersomes.The physicochemical characterizations of the nanoparticles such as morphology,the size and distribution,zeta potential,drug loading content,and encapsulation efficiency were also performed.Our results showed that polymeric micelles or polymersomes from PCEC both displayed narrow size distributions and could achieve high drug loading efficiencies.In vitro cellular uptake results suggested that Nile Red loaded polymeric micelles or polymersomes displayed more internalization after 24 h incubation than those after 4 h incubation.These findings suggest that polymeric micelles and polymersomes based on PCL-b-PEG-b-PCL copolymers have great potential to effectively delivery hydrophobic drugs.展开更多
The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be in...The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be inadequate to analyse the effect of each excipient and their potential interactions on the emulsion droplet size formed when dispersing the SNEDDS in an aqueous environment. The current study investigates the emulsion droplet sizes formed from SNEDDS containing different levels of the natural surfactant monoacyl phosphatidylcholine to reduce the concentration of the synthetic surfactant polyoxyl 40 hydrogenated castor oil(Kolliphor ~? RH40). Monoacyl phosphatidylcholine was used in the form of Lipoid S LPC 80(LPC, containing approximately 80% monoacyl phosphatidylcholine, 13% phosphatidylcholine and 4% concomitant components). The investigated SNEDDS comprised of long-chain or medium-chain glycerides(40% to 75%), Kolliphor ~? RH40(5% to 55%), LPC(0 to 40%) and ethanol(0 to 10%). D-optimal design, multiple linear regression, and partial least square regression were used to screen different SNEDDS within the investigated excipient ranges and to analyse the effect of each excipient on the resulting droplet size of the dispersed SNEDDS measured by dynamic light scattering. All investigated formulations formed nano-emulsions with droplet sizes from about 20 to 200 nm. The use of mediumchain glycerides was more likely to result in smaller and more monodisperse droplet sizes compared to the use of long-chain glycerides. Kolliphor~? RH40 exhibited the most significant effect on reducing the emulsion droplet sizes. Increasing LPC concentration increased the emulsion droplet sizes, possibly because of the reduction of Kolliphor~? RH40 concentration. A higher concentration of ethanol resulted in an insignificant reduction of the emulsion droplet size. The study provides different ternary diagrams of SNEDDS containing LPC and Kolliphor ~? RH40 as a reference for formulation developers.展开更多
Objective To develop an alternative method for assessment of gene delivery systems in vivo.Methods Mouse primary spleen lymphocytes were genetically modified in vitro by a retroviral vector harboring a Gaussia lucifer...Objective To develop an alternative method for assessment of gene delivery systems in vivo.Methods Mouse primary spleen lymphocytes were genetically modified in vitro by a retroviral vector harboring a Gaussia luciferase(Gluc) expression cassette.After implantation of these cells into recipient mice,the expression of Gluc was detected in whole blood or plasma collected.Results As little as 10 μL whole blood drawn from the recipient mice could guarantee prompt reading of Gluc activity with a luminometer.And the reading was found in good correlation with the number of genetically modified spleen lymphocytes implanted to the mice.Conclusions Gluc may be useful as an in vivo reporter for gene therapy researches,and Gluc blood assay could provide an alternative method for assessment of gene delivery systems in vivo.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.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82304443,82030107,and 82373944).
文摘Significant investment in nanocarrier drug delivery systems(Nano-DDSs)has yielded only a limited number of successfully marketed nanomedicines,highlighting a low rate of clinical translation.A primary contributing factor is the lack of foundational understanding of in vivo processes.Comprehensive knowledge of the pharmacokinetics of Nano-DDSs is essential for developing more efficacious nanomedicines and accurately evaluating their safety and associated risks.However,the complexity of Nano-DDSs has impeded thorough and systematic pharmacokinetic studies.Key components of pharmacokinetic investigations on Nano-DDSs include the analysis of the released drug,the encapsulated drug,and the nanomaterial,which present a higher level of complexity compared to traditional small-molecule drugs.Establishing an appropriate approach for monitoring the pharmacokinetics of Nano-DDSs is crucial for facilitating the clinical translation of nanomedicines.This review provides an overview of advanced bioanalytical methodologies employed in studying the pharmacokinetics of anticancer organic Nano-DDSs over the past five years.We hope that this review will enhance the understanding of the pharmacokinetics of Nano-DDSs and support the advancement of nanomedicines.
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 National Natural Science Foundation of China (Nos. 82374045, 82173985)the Jiangsu Province Leading Talent Project (No. CZ2023SLJ0302)+2 种基金the National Natural Science Foundation of China (No. 82173980)Jiangsu Province Key Research and Development Program for Social Development Project (No. BE2023788)the Jiangsu Clinical Innovation Center of Digestive Cancer of Traditional Chinese Medicine (No. 2021.6)。
文摘The treatment of tumors continues to be significantly challenging. The presence of multiple modalities, including surgery, radiation, chemotherapy and immunotherapy, the therapeutic outcomes remain limited and are often associated with adverse effects and inconsistent efficacy across cancer types. Recent studies have highlighted the potential of active components from traditional Chinese medicine(TCM) for their anti-cancer properties, which are attributable to multi-targeted mechanisms and broad pharmacological actions. Despite this potential, TCM-derived compounds are commonly limited by poor water solubility, low bioavailability, and suboptimal targeting. Currently, it is believed that advances in nanotechnology could address these limitations. Nanoparticles(NPs),which possess properties such as enhanced bioavailability, controlled release and precise targeting, have been used to improve the therapeutic efficacy of TCM components in cancer therapy. This review discusses the use of NPs for the delivery of active TCM compounds via organic-inorganic nanocarriers, highlighting innovative strategies that enhance the effectiveness of TCM-based anti-tumor components to provide insights into improving clinical outcomes while advancing the modernization and global application of TCM in oncology.
文摘Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity.These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems.The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems,and highlight the relationship between the properties and applications,and the effect of the species of phospholipids on the efficiency of drug delivery.We refer to some relevant literatures,starting from the structures,main sources and properties of phospholipids to introduce their applications in drug delivery systems.The present article focuses on introducing five types of carriers based on phospholipids,including liposomes,intravenous lipid emulsions,micelles,drug-phospholipids complexes and cochleates.
基金supported by the Chinese Natural Science Foundation Project (Grant No. 30970784 and 81171455)a National Distinguished Young Scholars Grant (Grant No. 31225009) from the National Natural Science Foundation of China+5 种基金the National Key Basic Research Program of China (Grant No. 2009CB930200)the Chinese Academy of Sciences (CAS) ‘Hundred Talents Program’ (Grant No. 07165111ZX)the CAS Knowledge Innovation Program, and the State HighTech Development Plan (Grant No. 2012AA020804)the ‘Strategic Priority Research Program’ of the Chinese Academy of Sciences (Grant No. XDA09030301)NIH/NIMHD 8 G12 MD007597USAMRMC W81XWH-10-1-0767 grants
文摘In the fight against cancer, controlled drug delivery systems have emerged to enhance the therapeutic efficacy and safety of anti-cancer drugs. Among these systems, mesoporous silica nanoparticles （MSNs） with a functional surface possess obvious advantages and were thus rapidly developed for cancer treatment. Many stimuli-responsive materials, such as nanopartides, polymers, and inorganic materials, have been applied as caps and gatekeepers to control drug release from MSNs. This review presents an overview of the recent progress in the production of pH-responsive MSNs based on the pH gradient between normal tissues and the tumor microenvironment. Four main categories of gatekeepers can respond to acidic conditions. These categories will be described in detail.
基金supported by grants from the National Natural Science Foundation of China(Nos.31922042 and 81771966)Science,Technology&Innovation Commission of Shenzhen Municipality(No.JCYJ20160531195129079)。
文摘Cancer is one of the diseases that have the highest mortality,which threatens the human health.Chemotherapy functions as the most widely used strategy in clinic to treat cancer,still exists urgent problems,like lacking selectivity and causing severe side effects.According to detailed researches on the metabolism,functions and histology of cancer tissues,many different features of cancer are uncovered,like lower pH in microenvironment,abnormal redox level in intracellular compartments and elevated expression level of several enzymes and receptors.Recently,the development of smart nanoparticles that response to tumor specific microenvironment has lighted up hope for selective cancer therapy.Herein,this review mainly focuses on pH-sensitive nano scale materials for anti-cancer drug delivery.We summarized the formation progress of acidic tumor microenvironment,the mechanism of pHresponsive drug delivery system and nanomaterials that responsive to acidic pH in tumor microenvironment.
文摘Since the discovery of the Nobel prize-winning mechanism of RNA interference(RNAi)ten years ago,it has become a promising drug target for the treatment of multiple diseases,including cancer.There have already been some successful applications of siRNA drugs in the treatment of age-related macular degeneration and respiratory syncytial virus infection.However,significant barriers still exist on the road to clinical applications of siRNA drugs,including poor cellular uptake,instability under physiological conditions,off-target effects and possible immunogenicity.The successful application of siRNA for cancer therapy requires the development of clinically suitable,safe and effective drug delivery systems.Herein,we review the design criteria for siRNA delivery systems and potential siRNA drug delivery systems for cancer therapy,including chemical modifications,lipidbased nanovectors,polymer-mediated delivery systems,conjugate delivery systems,and others.
基金National Basic Research Program of China(Grant No.973 Program,2013CB932500)National Natural Science Foundation of China(Grant No.81273458)Specialized Research Fund for the Doctoral Program of Higher Education(Grant No.20110071130011)
文摘In order to deliver and/or release anti-cancer therapeutics at the tumor sites, novel environment-responsive drug delivery systems are designed to specifically respond to tumor microenvironment （such as low pH and hypoxia）. Due to their extraordinary advantages, these environment-responsive drug delivery systems can improve antitumor efficacy, and most importantly, they can decrease toxicity associated with the anti-cancer therapeutics. This review highlights different mechanisms of environmentresponsive drug delivery systems and their applications for targeted cancer therapy.
文摘Inflammatory bowel disease(IBD)is a chronic illness characterized by relapsing inflammation of the intestines.The disorder is stratified according to the severity and is marked by its two main phenotypical representations:Ulcerative colitis and Crohn’s disease.Pathogenesis of the disease is ambiguous and is expected to have interactivity between genetic disposition,environmental factors such as bacterial agents,and dysregulated immune response.Treatment for IBD aims to reduce symptom extent and severity and halt disease progression.The mainstay drugs have been 5-aminosalicylates(5-ASAs),corticosteroids,and immunosuppressive agents.Parenteral,oral and rectal routes are the conventional methods of drug delivery,and among all,oral administration is most widely adopted.However,problems of systematic drug reactions and low specificity in delivering drugs to the inflamed sites have emerged with these regular routes of delivery.Novel drug delivery systems have been introduced to overcome several therapeutic obstacles and for localized drug delivery to target tissues.Enteric-coated microneedle pills,various nano-drug delivery techniques,prodrug systems,lipid-based vesicular systems,hybrid drug delivery systems,and biologic drug delivery systems constitute some of these novel methods.Microneedles are painless,they dislodge their content at the affected site,and their release can be prolonged.Recombinant bacteria such as genetically engineered Lactococcus Lactis and eukaryotic cells,including GM immune cells and red blood cells as nanoparticle carriers,can be plausible delivery methods when evaluating biologic systems.Nano-particle drug delivery systems consisting of various techniques are also employed as nanoparticles can penetrate through inflamed regions and adhere to the thick mucus of the diseased site.Prodrug systems such as 5-ASAs formulations or their derivatives are effective in reducing colonic damage.Liposomes can be modified with both hydrophilic and lipophilic particles and act as lipid-based vesicular systems,while hybrid drug delivery systems containing an internal nanoparticle section for loading drugs are potential routes too.Leukosomes are also considered as possible carrier systems,and results from mouse models have revealed that they control anti-and pro-inflammatory molecules.
基金supported by the National Natural Science Foundation of China (No.82073789)Innovative Research Group at Higher Educational Institutions in Chongqing (No.CXQT20006)。
文摘Extensive research has been performed on cell membrane camouflaged-based drug delivery systems in recent years.Herein,we provide an overview of the challenges in system preparation,functional design,continuous industrial production of these systems,and solution strategies for these challenges.Further,we analyze and discuss the frontier medical applications of cell membrane-camouflaged drug delivery systems in anti-inflammatory,anti-pathogenic microorganisms,and biological detoxification.This review takes a challenge-oriented perspective and seeks innovative strategies,provides a literature review of research into cell membrane-camouflaged drug delivery systems,and promotes the development of personalized clinical treatments.
基金Financial supports from the National Natural Science Foundation of China(Nos.31671024,51873228 and 31622025)the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2014218)+1 种基金the Fusion Grant between Fudan University and Shanghai Institute of Materia Medica,CAS(No.FU-SIMM20182006)the Open Project Program of Key Lab of Smart Drug Delivery(Ministry of Education),Department of Pharmaceutics,School of Pharmacy,Fudan University,China。
文摘Drug delivery systems(DDSs)are of paramount importance to deliver drugs at the intended targets,e.g.,tumor cells or tissue by prolonging blood circulation and optimizing the pharmaceutical profiles.However,the therapeutic efficacy of DDSs is severely impaired by insufficient or non-specific drug release.Dynamic chemical bonds having stimuli-liable prope rties are the refore introduced into DDSs for regulating the drug release kinetics.This review summarizes the recent advances of dynamic covalent chemistry in the DDSs for improving cancer therapy.The review discusses the constitutions of the major classes of dynamic covalent bonds,and the respective applications in the tumor-targe ted DDSs which are based on the different responsive mechanisms,including acid-activatable and reduction-activatable.Furthermore,the review also discusses combination strategies of dual dynamic covale nt bonds which can response to the complex tumor microenvironment much more accurately,and then summarizes and analyzes the prospects for the application of dynamic covalent chemistry in DDSs.
基金financial support from the Young Elite Scientists Sponsorship Program by Tianjin (No. 0701320001)Major Special Project of Tianjin (No. 0402080005)+1 种基金Program for Excellent Innovative Talents in Universities of Hebei Province (No. BJ2021019)Vietnam National University,Ho Chi Minh City (VNU-HCM,NCM2020-28-01)。
文摘Atherosclerosis(AS), mainly caused by the changed immune system functions and inflammation, is the central pathogenesis of cardiovascular disease, which is a leading cause of death in the world. In modern medicine, the development of carriers precisely delivering the therapeutic agents to the target sites is the primary goal, which could minimize the potential adverse effects and be more effective in treating lesions. Due to the precise location, real-time monitoring, AS microenvironment response, and low toxicity, stimuli-responsive nano-based drug delivery systems(NDDSs) have been a promising approach in AS treatments. Herein, we will systematically summarize the recent advances in stimuli-responsive NDDSs for AS treatment, including internal stimuli(reactive oxygen species, enzyme, shear stress, and pH) and external stimuli(light, ultrasound, and magnetism) responsive NDDSs. Besides, we will also summarize in detail the classification of stimuli-responsive NDDSs for AS, such as organic NDDSs(e.g., lipid-based and polymer-based nanomaterials), inorganic NDDSs(e.g., metal-based nanoparticles and nonmetallic nanomaterials), and composite multifunctional NDDSs. Finally, the critical challenges and prospects of this field will also be proposed and discussed.
文摘Since the start of the Precision Medicine Initiative by the United States of America in 2015,interest in personalized medicine has grown extensively.In short,personalized medicine is a term that describes medical treatment that is tuned to the individual.One possible way to realize personalized medicine is 3D printing.When using materials that can be tuned upon stimulation,4D printing is established.In recent years,many studies have been exploring a new field that combines 3D and 4D printing with therapeutics.This has resulted in many concepts of pharmaceutical devices and formulations that can be printed and,possibly,tailored to an individual.Moreover,the first 3D printed drug,Spritam®,has already found its way to the clinic.This review gives an overview of various 3D and 4D printing techniques and their applications in the pharmaceutical field as drug delivery systems and personalized medicine.
文摘Gene therapy has shown great potential to treat various diseases by repairing the abnormal gene function.However,a great challenge in bringing the nucleic acid formulations to the market is the safe and effective delivery to the specific tissues and cells.To be excited,the development of ionizable drug delivery systems(IDDSs)has promoted a great breakthrough as evidenced by the approval of the BNT162b2 vaccine for prevention of coronavirus disease 2019(COVID-19)in 2021.Compared with conventional cationic gene vectors,IDDSs can decrease the toxicity of carriers to cell membranes,and increase cellular uptake and endosomal escape of nucleic acids by their unique pH-responsive structures.Despite the progress,there remain necessary requirements for designing more efficient IDDSs for precise gene therapy.Herein,we systematically classify the IDDSs and summarize the characteristics and advantages of IDDSs in order to explore the underlying design mechanisms.The delivery mechanisms and therapeutic applications of IDDSs are comprehensively reviewed for the delivery of plasmid DNA(pDNA)and four kinds of RNA.In particular,organ selecting considerations and high-throughput screening are highlighted to explore efficiently multifunctional ionizable nanomaterials with superior gene delivery capacity.We anticipate providing references for researchers to rationally design more efficient and accurate targeted gene delivery systems in the future,and indicate ideas for developing next generation gene vectors.
基金Supported by Science and Health Joint Medical Research Project of Chongqing,No.2022MSXM133Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522,No.CSTB2023NSCQ-MSX0246,No.CSTB2022NSCQ-MSX1271+1 种基金The First Batch of Key Disciplines on Public Health in Chongqing and ScienceHealth Joint Project of Dazu District Science and Technology Bureau,No.DZKJ,2022CCC1001.
文摘The complication of diabetes,which is known as diabetic foot ulcer(DFU),is a significant concern due to its association with high rates of disability and mortality.It not only severely affects patients’quality of life,but also imposes a substantial burden on the healthcare system.In spite of efforts made in clinical practice,treating DFU remains a challenging task.While mesenchymal stem cell(MSC)therapy has been extensively studied in treating DFU,the current efficacy of DFU healing using this method is still inadequate.However,in recent years,several MSCs-based drug delivery systems have emerged,which have shown to increase the efficacy of MSC therapy,especially in treating DFU.This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.
基金the National Natural Science Foundation of China (Nos. 21272093 and 51473061)the Fundamental Research Funds for the Central Universities (No. JCKY-QKJC05) for financial support
文摘In recent years, cancer has become the number two cause of death around the world, and scientists have exploited various treatment maps. Calixarenes, with diversified features, have been widely applied into drug delivery systems, which can respond to multi-stimuli and exhibit excellent performance. In this mini-review, we summarize the recent advances on controlled drug delivery systems based on calixarenes, in the form of inclusion complexes, amphiphilic self-assembly nanocarriers including micelles, hydrogels, vesicles and liposomes, and supramolecular nanovalves on mesoporous silica nanomaterials.
基金supported by National Natural Science Foundation of China(Nos.81571793,81671806 and 51373199)CAMS Innovation Fund for Medical Sciences,Tianjin Municipal Natural Science Foundation(No.15JCZDJC38300)Science and Technology Support Program of Tianjin(No.15RCGFSY00146)
文摘Polye-caprolactone）-b-poly（ethylene glycol）-b-poly（e-caprolactone）（PCL-b-PEG-b-PCL,PCEC） triblock copolymers have been widely investigated in last several decades.Here,by altering the weight ratio of monomers in ring-opening polymerization,a series of PCEC triblock copolymers with varying hydrophobicity were synthesized,which were characterized by FTIR,1 H NMR,GPC and DSC.When PCEC copolymers with different weight ratios of PCL/PEG were dispersed in different aqueous solutions,they could self-assemble and form two distinctive nanoparticular structures：micelles or polymersomes.We then chose paclitaxel（PTX） as the model drug and encapsulate PTX into PCEC polymeric micelles and polymersomes.The physicochemical characterizations of the nanoparticles such as morphology,the size and distribution,zeta potential,drug loading content,and encapsulation efficiency were also performed.Our results showed that polymeric micelles or polymersomes from PCEC both displayed narrow size distributions and could achieve high drug loading efficiencies.In vitro cellular uptake results suggested that Nile Red loaded polymeric micelles or polymersomes displayed more internalization after 24 h incubation than those after 4 h incubation.These findings suggest that polymeric micelles and polymersomes based on PCL-b-PEG-b-PCL copolymers have great potential to effectively delivery hydrophobic drugs.
基金Financial support from the University of Copenhagen and the Phospholipid Research Center(Heidelberg,Germany)is kindly acknowledged
文摘The development of self-nanoemulsifying drug delivery systems(SNEDDS) to enhance the oral bioavailability of lipophilic drugs is usually based on traditional one-factor-at-a-time approaches. These approaches may be inadequate to analyse the effect of each excipient and their potential interactions on the emulsion droplet size formed when dispersing the SNEDDS in an aqueous environment. The current study investigates the emulsion droplet sizes formed from SNEDDS containing different levels of the natural surfactant monoacyl phosphatidylcholine to reduce the concentration of the synthetic surfactant polyoxyl 40 hydrogenated castor oil(Kolliphor ~? RH40). Monoacyl phosphatidylcholine was used in the form of Lipoid S LPC 80(LPC, containing approximately 80% monoacyl phosphatidylcholine, 13% phosphatidylcholine and 4% concomitant components). The investigated SNEDDS comprised of long-chain or medium-chain glycerides(40% to 75%), Kolliphor ~? RH40(5% to 55%), LPC(0 to 40%) and ethanol(0 to 10%). D-optimal design, multiple linear regression, and partial least square regression were used to screen different SNEDDS within the investigated excipient ranges and to analyse the effect of each excipient on the resulting droplet size of the dispersed SNEDDS measured by dynamic light scattering. All investigated formulations formed nano-emulsions with droplet sizes from about 20 to 200 nm. The use of mediumchain glycerides was more likely to result in smaller and more monodisperse droplet sizes compared to the use of long-chain glycerides. Kolliphor~? RH40 exhibited the most significant effect on reducing the emulsion droplet sizes. Increasing LPC concentration increased the emulsion droplet sizes, possibly because of the reduction of Kolliphor~? RH40 concentration. A higher concentration of ethanol resulted in an insignificant reduction of the emulsion droplet size. The study provides different ternary diagrams of SNEDDS containing LPC and Kolliphor ~? RH40 as a reference for formulation developers.
基金Supported by National High Technology Research and Development Program of China (863 Program) (2007AA021206,2007AA021106)
文摘Objective To develop an alternative method for assessment of gene delivery systems in vivo.Methods Mouse primary spleen lymphocytes were genetically modified in vitro by a retroviral vector harboring a Gaussia luciferase(Gluc) expression cassette.After implantation of these cells into recipient mice,the expression of Gluc was detected in whole blood or plasma collected.Results As little as 10 μL whole blood drawn from the recipient mice could guarantee prompt reading of Gluc activity with a luminometer.And the reading was found in good correlation with the number of genetically modified spleen lymphocytes implanted to the mice.Conclusions Gluc may be useful as an in vivo reporter for gene therapy researches,and Gluc blood assay could provide an alternative method for assessment of gene delivery systems in vivo.
