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
Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contr...Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.展开更多
With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of res...With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.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
Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherap...Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.展开更多
Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a ty...Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.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
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
This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazola...This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.展开更多
Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease ...Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease is associated with dementia and a progressive decline in memory,thinking,and social skills,eventually leading to a point that the individual can no longer perform daily activities independently.Currently available drugs on the market temporarily alleviate the symptoms,however,they are not successful in slowing down the progression of Alzheimer’s disease.Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier.Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications.Recently,liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier.Liposomes are being used as a component of nanoparticle drug delivery;due to their biocompatible nature;and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells.Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders.The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment.Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s disease.This review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain,and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s disease.This review also sheds some light on variation of liposomes.Additionally,it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer’s disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer’s disease.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
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
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
This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindnes...This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindness worldwide.Advanced AMD can be classified into two subtypes:late-stage dry AMD[known as geographic atrophy(GA)]and neovascular AMD(nAMD).GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium.Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium(RPE)or retina,a process known as choroidal neovascularization(CNV).Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD.Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD.Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies.Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems,including hydrogels,microparticles,nanoparticles,implants,and liposomes.Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations.New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment.展开更多
Deep space communication has its own features such as long propagation delays,heavy noise,asymmetric link rates,and intermittent connectivity in space,therefore TCP/IP protocol cannot perform as well as it does in ter...Deep space communication has its own features such as long propagation delays,heavy noise,asymmetric link rates,and intermittent connectivity in space,therefore TCP/IP protocol cannot perform as well as it does in terrestrial communications.Accordingly,the Consultative Committee for Space Data Systems(CCSDS) developed CCSDS File Delivery Protocol(CFDP),which sets standards of efficient file delivery service capable of transferring files to and from mass memory located in the space segment.In CFDP,four optional acknowledge modes are supported to make the communication more reliable.In this paper,we gave a general introduction of typical communication process in CFDP and analysis of its four Negative Acknowledgement(NAK) modes on the respect of file delivery delay and times of retransmission.We found out that despite the shortest file delivery delay,immediate NAK mode suffers from the problem that frequent retransmission may probably lead to network congestion.Thus,we proposed a new mode,the error counter-based NAK mode.By simulation of the case focused on the link between a deep space probe on Mars and a ter-restrial station on Earth,we concluded that error counter-based NAK mode has successfully reduced the retransmission times at negligible cost of certain amount of file delivery delay.展开更多
Transdermal drug delivery systems(TDDs)have the advantages on good local targeting,controlled and sustainable drug delivery.Hoewever,the stratum corneum,as the main skin barrier,severely limits the transdermal penetra...Transdermal drug delivery systems(TDDs)have the advantages on good local targeting,controlled and sustainable drug delivery.Hoewever,the stratum corneum,as the main skin barrier,severely limits the transdermal penetration of drugs and reduces bioavailability,which also limits their application.Microneedles(MNS)penetrate the stratum corneum and create several reversible microchannels in a minimally invasive manner to significantly improve the penetration of therapeutic agents,and are considered a milestone for effective transdermal drug delivery.As an emerging drug delivery modality,microneedle transdermal drug delivery systems have the advantages of being minimally invasive,safe,efficient,economical and convenient.In addition to the extensive research on microneedles for improving transdermal drug delivery,there is a growing interest in using them to manage and treat dermatological conditions.Being the largest organ in the human body,the skin acts as a barrier between the body and the external environment,while having an immense influence on appearance and self-confidence.Indeed,there is now a considerable body of evidence on how dermatological conditions can lead to psychological problems and a reduced quality of life.The utilisation of microneedle transdermal drug delivery systems for the management and treatment of dermatological conditions is of great therapeutic and commercial value.The principleof microneedle transdermal drug delivery systems and the progress of its clinical application in dermatology are reviewed here.展开更多
Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity...Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens.Omiganan,an antimicrobial peptide,has shown promise for neutralizing endotoxins and eliminating diverse pathogens.However,its clinical application is hindered by safety and stability concerns.Herein,we present a nanoscale drug delivery system(Omi-hyd-Dex@HA NPs)that selectively targets infectious microenvironments(IMEs)and responds to specific stimuli for efficient intervention in sepsis.The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid(HA).The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes,but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase.The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation.In multiple tissue infection and sepsis animal models,Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction,thereby preventing subsequent fatal complications and significantly improving survival outcomes.The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.展开更多
Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their sel...Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.展开更多
Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poo...Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy.Fortunately,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance.Therefore,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy.We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses.Furthermore,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also emphasized.DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.展开更多
The aqueous two-phase system(ATPS)is an all-aqueous system fabricated from two immiscible aqueous phases.It is spontaneously assembled through physical liquid-liquid phase separation(LLPS)and can create suitable templ...The aqueous two-phase system(ATPS)is an all-aqueous system fabricated from two immiscible aqueous phases.It is spontaneously assembled through physical liquid-liquid phase separation(LLPS)and can create suitable templates like the multicompartment of the intracellular environment.Delicate structures containing multiple compartments make it possible to endow materials with advanced functions.Due to the properties of ATPSs,ATPS-based drug delivery systems exhibit excellent biocompatibility,extraordinary loading efficiency,and intelligently controlled content release,which are particularly advantageous for delivering drugs in vivo.Therefore,we will systematically review and evaluate ATPSs as an ideal drug delivery system.Based on the basic mechanisms and influencing factors in forming ATPSs,the transformation of ATPSs into valuable biomaterials is described.Afterward,we concentrate on the most recent cutting-edge research on ATPS-based delivery systems.Finally,the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.展开更多
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by the National Natural Science Foundation of China(No.81700453).
文摘Current treatments for advanced hepatocellular carcinoma(HCC)have limited success in improving patients’quality of life and prolonging life expectancy.The clinical need for more efficient and safe therapies has contributed to the exploration of emerging strategies.Recently,there has been increased interest in oncolytic viruses(OVs)as a therapeutic modality for HCC.OVs undergo selective replication in cancerous tissues and kill tumor cells.Strikingly,pexastimogene devacirepvec(Pexa-Vec)was granted an orphan drug status in HCC by the U.S.Food and Drug Administration(FDA)in 2013.Meanwhile,dozens of OVs are being tested in HCC-directed clinical and preclinical trials.In this review,the pathogenesis and current therapies of HCC are outlined.Next,we summarize multiple OVs as single therapeutic agents for the treatment of HCC,which have demonstrated certain efficacy and lowtoxicity.Emerging carrier cell-,bioengineered cell mimetic-or nonbiological vehicle-mediated OV intravenous delivery systems in HCC therapy are described.In addition,we highlight the combination treatments between oncolytic virotherapy and other modalities.Finally,the clinical challenges and prospects of OV-based biotherapy are discussed,with the aim of continuing to develop a fascinating approach in HCC patients.
基金Hainan Innovation Team Project of Hainan(820CXTD448)Hainan Province Key R&D Program International Science and Technology Cooperation Project(GHYF2022011)+8 种基金Key R&D Projects in Hainan ProvincZDYF2020223Hainan Provincial Major Science and Technology Project(ZDKJ2021036)Hainan Provincial Natural Science Foundation of High-level Talent Project 2019RC212Chinese Academy of Medical Sciences Medical and Health Science and Technology Innovation Engineering Project(2019-12M-5-023)Major Science and Technology Project of Hainan Province(ZDKJ2021039,ZDKJ202004)Key Topics of Hainan Medical College's Educational and Scientific Research Projects(HYZD202111)National Natural Science Foundation of China(81860001,82011530049 and 82160012)Open Project of the Key Laboratory of Tropical Disease Prevention and Control of the NHC(2021NHCTDCKFKT21008)Hainan Provincial Clinical Medical Center Construction Project Fund。
文摘With the influence of many factors such as the aging of the population,the younger smokers,and the serious air pollution,the incidence of chronic respiratory diseases is increasing year by year.In the treatment of respiratory diseases,clinical intervention is still mainly based on drug control of pulmonary symptoms.However,systemic drugs have disadvantages such as many adverse reactions and severe systemic side effects.In recent years,the research and development of local drug delivery systems for the respiratory tract has brought new changes to the treatment of respiratory diseases.Locally delivered drugs can directly act on the airways and have the characteristics of fast onset,good curative effect and small side effects.It is a simple,efficient and safe treatment method,which has a very significant effect,and has become a hot topic of current research and promotion.This paper briefly reviews the development track and latest research progress of respiratory local drug delivery systems at home and abroad,in order to provide reference for clinical workers in drug selection and application.
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supported by the National Research Foundation of Korea(NRF)grant funded by the Ministry of Science and ICT(MSIT)(No.2021R1A2C2012808)Technology Innovation Program(Alchemist Project)(No.20012378)funded by the Ministry of Trade,Industry&Energy(MOTIE),South Korea.
文摘Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.
文摘Colorectal cancer(CRC)is a form of cancer that is often resistant to chemotherapy,targeted therapy,radiotherapy,and immunotherapy due to its genomic instability and inflammatory tumor microenvironment.Ferroptosis,a type of non-apoptotic cell death,is characterized by the accumulation of iron and the oxidation of lipids.Studies have revealed that the levels of reactive oxygen species and glutathione in CRC cells are significantly lower than those in healthy colon cells.Erastin has emerged as a promising candidate for CRC treatment by diminishing stemness and chemoresistance.Moreover,the gut,responsible for regulating iron absorption and release,could influence CRC susceptibility through iron metabolism modulation.Investigation into ferroptosis offers new insights into CRC pathogenesis and clinical management,potentially revolutionizing treatment approaches for therapy-resistant cancers.
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.
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supported by a grant from National Natural Sciences Foundation of China (No.30873171)
文摘This study examined the effect of self-microemulsiflying drug delivery system (SMEDDS) containing Cremophor RH40 or Tween 80 at various dilutions on cytochrome P450 3A (CYP3A) enzymes in rat hepatocytes, with midazolam serving as a CYP3A substrate.The particle size and zeta potential of microemulsions were evaluated upon dilution with aqueous medium.In vitro release was detected by a dialysis method in reverse.The effects of SMEDDS at different dilutions and surfactants at different concentrations on the metabolism of MDZ were investigated in murine hepatocytes.The cytotoxicity of SMEDDS at different dilutions was measured by LDH release and MTT technique.The effects of SMEDDS on the CYP3A enzymes activity were determined by Western blotting.Our results showed that dilution had less effect on the particle size and zeta potential in the range from 1:25 to 1:500.The MDZ was completely released in 10 h.A significant decrease in the formation of 1’-OH-MDZ in rat hepatocytes was observed after treatment with both SMEDDS at dilutions ranging from 1:50 to 1:250 and Cremophor RH 40 or Tween 80 at concentrations ranging from 0.1% to 1% (w/v), with no cytotoxicity observed.A significant decrease in CYP3A protein expression was observed in cells by Western blotting in the presence of either Cremophor RH40 or Tween 80-based SMEDDS at the dilutions ranging from 1:50 to 1:250.This study suggested that the excipient inhibitor-based formulation is a potential protective platform for decreasing metabolism of sensitive drugs that are CYP3A substrates.
文摘Alzheimer’s disease is a neurodegenerative condition leading to atrophy of the brain and robbing nearly 5.8 million individuals in the United States age 65 and older of their cognitive functions.Alzheimer’s disease is associated with dementia and a progressive decline in memory,thinking,and social skills,eventually leading to a point that the individual can no longer perform daily activities independently.Currently available drugs on the market temporarily alleviate the symptoms,however,they are not successful in slowing down the progression of Alzheimer’s disease.Treatment and cures have been constricted due to the difficulty of drug delivery to the blood-brain barrier.Several studies have led to identification of vesicles to transport the necessary drugs through the blood-brain barrier that would typically not achieve the targeted area through systemic delivered medications.Recently,liposomes have emerged as a viable drug delivery agent to transport drugs that are not able to cross the blood-brain barrier.Liposomes are being used as a component of nanoparticle drug delivery;due to their biocompatible nature;and possessing the capability to carry both lipophilic and hydrophilic therapeutic agents across the blood brain barrier into the brain cells.Studies indicate the importance of liposomal based drug delivery in treatment of neurodegenerative disorders.The idea is to encapsulate the drugs inside the properly engineered liposome to generate a response of treatment.Liposomes are engineered to target specific diseased moieties and also several surface modifications of liposomes are under research to create a clinical path to the management of Alzheimer’s disease.This review deals with Alzheimer’s disease and emphasize on challenges associated with drug delivery to the brain,and how liposomal drug delivery can play an important role as a drug delivery method for the treatment of Alzheimer’s disease.This review also sheds some light on variation of liposomes.Additionally,it emphasizes on the liposomal formulations which are currently researched or used for treatment of Alzheimer’s disease and also discusses the future prospect of liposomal based drug delivery in Alzheimer’s disease.
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.
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.
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.
文摘This narrative review highlights routes of ocular drug delivery for age-related macular degeneration(AMD).AMD is the leading cause of irreversible blindness in industrialized countries and accounts for 8.7%of blindness worldwide.Advanced AMD can be classified into two subtypes:late-stage dry AMD[known as geographic atrophy(GA)]and neovascular AMD(nAMD).GA is often bilateral and results from progressive and irreversible loss of photoreceptors and areas of the retinal pigment epithelium.Wet AMD is characterized by angiogenesis from the choroid to the normally avascular regions underneath the retinal pigment epithelium(RPE)or retina,a process known as choroidal neovascularization(CNV).Various targeted therapeutic options are currently available to reduce the progression rate and maintain vision in patients with nAMD.Intravitreal delivery of anti-VEGF protein treatments to halt CNV is currently the gold-standard of care for nAMD.Subretinal and suprachoroidal delivery approaches are also being explored for gene and molecular therapies.Advancements in nanotechnology and biomaterials have also led to the development of microscopic drug delivery systems,including hydrogels,microparticles,nanoparticles,implants,and liposomes.Gene therapy and stem cell therapy has recently emerged as a potential candidate treatment modality for AMD and other retinal degenerations.New drug targets and modalities have stimulated exciting developments in ocular drug delivery with the promise of greater efficacy and durability of AMD treatment.
文摘Deep space communication has its own features such as long propagation delays,heavy noise,asymmetric link rates,and intermittent connectivity in space,therefore TCP/IP protocol cannot perform as well as it does in terrestrial communications.Accordingly,the Consultative Committee for Space Data Systems(CCSDS) developed CCSDS File Delivery Protocol(CFDP),which sets standards of efficient file delivery service capable of transferring files to and from mass memory located in the space segment.In CFDP,four optional acknowledge modes are supported to make the communication more reliable.In this paper,we gave a general introduction of typical communication process in CFDP and analysis of its four Negative Acknowledgement(NAK) modes on the respect of file delivery delay and times of retransmission.We found out that despite the shortest file delivery delay,immediate NAK mode suffers from the problem that frequent retransmission may probably lead to network congestion.Thus,we proposed a new mode,the error counter-based NAK mode.By simulation of the case focused on the link between a deep space probe on Mars and a ter-restrial station on Earth,we concluded that error counter-based NAK mode has successfully reduced the retransmission times at negligible cost of certain amount of file delivery delay.
基金Yunnan Provincial Science and Technology Department University Joint Project:Effect and mechanism of microneedle transdermal administration of Periplaneta Americana extract on aging skin of mice(202001BA070001-214).
文摘Transdermal drug delivery systems(TDDs)have the advantages on good local targeting,controlled and sustainable drug delivery.Hoewever,the stratum corneum,as the main skin barrier,severely limits the transdermal penetration of drugs and reduces bioavailability,which also limits their application.Microneedles(MNS)penetrate the stratum corneum and create several reversible microchannels in a minimally invasive manner to significantly improve the penetration of therapeutic agents,and are considered a milestone for effective transdermal drug delivery.As an emerging drug delivery modality,microneedle transdermal drug delivery systems have the advantages of being minimally invasive,safe,efficient,economical and convenient.In addition to the extensive research on microneedles for improving transdermal drug delivery,there is a growing interest in using them to manage and treat dermatological conditions.Being the largest organ in the human body,the skin acts as a barrier between the body and the external environment,while having an immense influence on appearance and self-confidence.Indeed,there is now a considerable body of evidence on how dermatological conditions can lead to psychological problems and a reduced quality of life.The utilisation of microneedle transdermal drug delivery systems for the management and treatment of dermatological conditions is of great therapeutic and commercial value.The principleof microneedle transdermal drug delivery systems and the progress of its clinical application in dermatology are reviewed here.
基金supported by the Program of the Scientific and Technological in Guiyang City(Grant No.Zhu Ke He[2020]-16-5)Program of Scientific and Technological Project in Guizhou Province(Grant No.[2020]4Y197,Qian Ke He Ji Chu ZK[2022]Yi Ban 516,Qian Ke He Ji Chu ZK[2021]Yi Ban 559)+3 种基金the Science and Technology Talents Growth Project in Education Department of Guizhou Province(Grant No.Qian Jiao He KY Zi[2021]4Y211)the Program of Science and Technology of Guizhou Provincial Health Commission(Grant No.gzwjkj2020-1-215)the Knowledge Innovation Special Project for Fundamental Research of Wuhan(Grant No.2022020801010461)the Sichuan Science and Technology Program(Grant No.2022NSFSC1420).
文摘Sepsis is a life-threatening emergency that causes millions of deaths every year due to severe infection and inflammation.Nevertheless,current therapeutic regimens are inadequate to promptly address the vast diversity of potential pathogens.Omiganan,an antimicrobial peptide,has shown promise for neutralizing endotoxins and eliminating diverse pathogens.However,its clinical application is hindered by safety and stability concerns.Herein,we present a nanoscale drug delivery system(Omi-hyd-Dex@HA NPs)that selectively targets infectious microenvironments(IMEs)and responds to specific stimuli for efficient intervention in sepsis.The system consists of omiganan-dexamethasone conjugates linked by hydrazone bonds which self-assemble into nanoparticles coated with a hyaluronic acid(HA).The HA coating not only facilitates IMEs-targeting through interaction with intercellular-adhesion-molecule-1 on inflamed endotheliocytes,but also improves the biosafety of the nanosystem and enhances drug accumulation in primary infection sites triggered by hyaluronidase.The nanoparticles release dual drugs in IMEs through pH-sensitive cleavage of hydrazone bonds to eradicate pathogens and suppress inflammation.In multiple tissue infection and sepsis animal models,Omi-hyd-Dex@HA NPs exhibited rapid source control and comprehensive inflammation reduction,thereby preventing subsequent fatal complications and significantly improving survival outcomes.The bio-responsive and self-delivering nanosystem offers a promising strategy for systemic sepsis treatment in emergencies.
基金Natural Science Foundation of Nanjing University of Chinese Medicine China,No.XZR2020093.
文摘Cancer stem cells(CSCs)are a small proportion of the cells that exist in cancer tissues.They are considered to be the culprit of tumor genesis,development,drug resistance,metastasis and recurrence because of their self-renewal,proliferation,and differentiation potential.The elimination of CSCs is thus the key to cure cancer,and targeting CSCs provides a new method for tumor treatment.Due to the advantages of controlled sustained release,targeting and high biocompatibility,a variety of nanomaterials are used in the diagnosis and treatments targeting CSCs and promote the recognition and removal of tumor cells and CSCs.This article mainly reviews the research progress of nanotechnology in sorting CSCs and nanodrug delivery systems targeting CSCs.Furthermore,we identify the problems and future research directions of nanotechnology in CSC therapy.We hope that this review will provide guidance for the design of nanotechnology as a drug carrier so that it can be used in clinic for cancer therapy as soon as possible.
基金financial support from the National Natural Science Foundation of China(Nos.U21A20417,31930067,and 31800797)the Sichuan Science and Technology Program(Nos.2022YFS0333 and 2022YFS0203)+1 种基金the 1·3·5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18002)the Post-Doctor Research Project,West China Hospital,Sichuan University(No.2018HXBH066)。
文摘Colorectal cancer causes the third most common type of malignant tumors with high morbidity and mortality.Chemotherapy is currently one of the most effective and common treatments for colorectal cancer.However,the poor water solubility of some chemotherapeutics,untargeted drug delivery,and the undesirable systemic side effects of conventional treatment remain the major issues for colorectal cancer chemotherapy.Fortunately,drug delivery systems(DDS)based on biomaterials have been widely investigated and found to be capable of resolving those issues with good performance.Therefore,the main goal of this review is to summarize and discuss the progress and potential advantages of different DDS for colorectal cancer chemotherapy.We not only reviewed the nanocarriers used to improve the solubility of chemotherapeutics,including liposomes,micelles,and nanoparticles,but also discussed targeted DDS based on specific ligand-receptor recognition and tumor microenvironmental stimulus responses.Furthermore,locally administered systems based on hydrogels and microspheres,which have been shown to increase drug accumulation at the tumor site while decreasing systemic toxicity,were also emphasized.DDS provides a good option for improving the efficacy of chemotherapy in the treatment of colorectal cancer.
基金This study was supported by National Natural Science Foundation of China Youth Science Fund Project(Grant number 82001107)the Applied Basic Research Project of Sichuan province(Grant number 2022NSFSC1345,China).
文摘The aqueous two-phase system(ATPS)is an all-aqueous system fabricated from two immiscible aqueous phases.It is spontaneously assembled through physical liquid-liquid phase separation(LLPS)and can create suitable templates like the multicompartment of the intracellular environment.Delicate structures containing multiple compartments make it possible to endow materials with advanced functions.Due to the properties of ATPSs,ATPS-based drug delivery systems exhibit excellent biocompatibility,extraordinary loading efficiency,and intelligently controlled content release,which are particularly advantageous for delivering drugs in vivo.Therefore,we will systematically review and evaluate ATPSs as an ideal drug delivery system.Based on the basic mechanisms and influencing factors in forming ATPSs,the transformation of ATPSs into valuable biomaterials is described.Afterward,we concentrate on the most recent cutting-edge research on ATPS-based delivery systems.Finally,the potential for further collaborations between ATPS-based drug-carrying biomaterials and disease diagnosis and treatment is also explored.