In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which partici...In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.展开更多
Online Food Delivery Platforms(OFDPs)has witnessed phenomenal growth in the past few years,especially this year due to the COVID-19 pandemic.This Pandemic has forced many governments across the world to give momentum ...Online Food Delivery Platforms(OFDPs)has witnessed phenomenal growth in the past few years,especially this year due to the COVID-19 pandemic.This Pandemic has forced many governments across the world to give momentum to OFD services and make their presence among the customers.The Presence of several multinational and national companies in this sector has enhanced the competition and companies are trying to adapt various marketing strategies and exploring the brand experience(BEX)dimension that helps in enhancing the brand equity(BE)of OFDPs.BEXs are critical for building brand loyalty(BL)and making companies profitable.Customers can experience different kinds of brand experiences through feeling,emotions,affection,behavior,and intellect.The present research work is taken up to analyze the factors affecting BEX and its impact on BL and BE of the OFDPs and analyze the mediating role of BL in the relationship between BEX and BE of the OFDPs in the Indian context.A survey of 457 Indian customers was carried out.A questionnaire was used for data collection and a mediation study was used to test hypothesized relationships.Our computational analysis reveals that BEX influences the BL and BE of OFDPs.The study further indicates that BL mediates the relationship between BEX and BE of OFDPs.The effective marketing and relationship management practices will help company to enhance BEX that will enable in enhancing BL and raising BE of their product.It therefore provides a more thorough analysis of BEX constructs and their consequences than previous research.Some of the managerial implication,limitations,and scope of future research are also presented in the study.展开更多
Oracle and ZTE announced on April 21, 2008 that they have extended their alliance in connection with the marketing and development of Service Delivery Platform offerings in China and globally.
The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines.The integration of novel drug design and synthesis techniques,display library technology,delivery ...The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines.The integration of novel drug design and synthesis techniques,display library technology,delivery systems,bioengineering advancements,and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs,effectively addressing the obstacles associated with their character,such as the rapid clearance and degradation,necessitating subcutaneous injection leading to increasing patient discomfort,and ultimately advancing translational research efforts.Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions,such as diabetes mellitus,weight loss,oncology,and rare diseases,and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines.This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics,delivery platforms,and vaccines.It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs,as well as the recent advancements in screening,design,and delivery technologies.The accelerated advancement in the development of novel peptide-based therapeutics,including peptide-drug complexes,new peptide-based vaccines,and innovative peptide-based diagnostic reagents,has the potential to promote the era of precise customization of disease therapeutic schedule.展开更多
Drug distribution in cells depends on the partition nature determined by its chemical structure,which could influence drug concentration and efficacy.Conversely,precise delivery of a drug to the specific condensates i...Drug distribution in cells depends on the partition nature determined by its chemical structure,which could influence drug concentration and efficacy.Conversely,precise delivery of a drug to the specific condensates in cells,such as organelles,means a distinct way to remodel the drug action.We here introduce an unprecedented molecular delivery platform with an accurate loading capacity of a drug,able to simultaneously target mitochondria(Mito)and endoplasmic reticulum(ER)while releasing the parent drug in situ.For our proof of concept,we used desloratadine(Des),a common anti-allergic drug,as the parent drug to develop a delivery platform(DDY)for chemotherapy.DDY can respond to the glutathione(GSH)levels,allowing for the selective release of Des in Mito and ER in cancer cells,which have higher GSH concentrations than normal cells.The release of Des in Mito and ER effectively and selectively induces tumor cells to ferroptosis while causing minimal toxicity to normal cells.DDY exhibits a satisfied chemotherapy efficacy in xenograft and metastasis cancer models,which should originate from the effects of Des in the two organelles.The result demonstrates the potential for developing chemotherapy from a currently approved drug with little anti-cancer activity through a precise distribution of it to organelles,significantly broadening the space of drug candidates for future chemotherapy.展开更多
Exosomes,a specific subset of extracellular vesicles,have diverse functions in various biological processes.In the field of cancer research,there has been a growing interest in the potential of exosomes to act as vers...Exosomes,a specific subset of extracellular vesicles,have diverse functions in various biological processes.In the field of cancer research,there has been a growing interest in the potential of exosomes to act as versatile vehicles for targeted tumor imaging and therapy.In this study,we constructed a targeted delivery platform using hypoimmunogenic exosomes by genetically modifyingβ2-microglobulin knocking-out HEK-293F cells to express a fusion protein,referred to asαMUC1-Exo,which comprises the exosomal membrane-enriched platelet-derived growth factor receptor,intracellular nanoluciferase,and extracellular anti-MUC1 single-chain variable fragment.The findings of this study indicate thatαMUC1-Exos exhibited notable drug delivery properties toward MUC1-positive pancreatic cancer cells,resulting in a substantial inhibition of tumor growth.Moreover,these exosomes demon-strated a high level of biosafety and the absence of any adverse effects.The application of engineered exosomes as a vehicle for drug delivery holds promise for enhancing the immunogenicity of neoplastic cells following treatment,thereby inducing antitumor immune memory in mice with intact immune systems,and also improving the response to anti-PD1 therapy.This approach utilizing engineered exosomes for Gemcitabine administration holds promise as a potential strategy for overcoming drug resistance in pancreatic carcinoma thereby improving the overall treatment efficacy.展开更多
Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilay...Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs,improving drug stability and solubility as well as providing increased bioavailability,reduced systemic toxicity,and enhanced target accumulation.Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting,controlled drug release,and massive production.Meanwhile,they are capable of crossing the blood-brain barrier(BBB)to transport the cargo to the lesion sites without harboring human pathogens,making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases.Herein,this article provides an initial exposition on the fundamental characteristics of PDNVs,including biogenesis,uptake process,isolation,purification,characterization methods,and source.Additionally,it sheds light on the investigation of PDNVs’utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.展开更多
In recent years,two pricing policies are commonly adopted by on-demand delivery service platforms(e.g,Meituan PaoTui and Costco)that provide delivery services to heterogeneous customers via self-scheduling providers.O...In recent years,two pricing policies are commonly adopted by on-demand delivery service platforms(e.g,Meituan PaoTui and Costco)that provide delivery services to heterogeneous customers via self-scheduling providers.One called"transaction-based"pricing policy(TBPP)allows the platforms to determine a per-service wage paid to providers and a price charged to customers for each transaction.The other one called"membership-based"pricing policy(MBPP)also allows the platforms to announce a wage paid to providers but charge customers a membership fee for using an unlimited number of the services in a certain period(e.g.,one month).This paper considers an on-demand delivery service platform with self-scheduling providers and two classes of customers(i.e.,regular and frequent customers).We aim to analyze and compare the platform's profits and welfare performances generated by the two pricing policies.If the number of regular customers and their preference for TBPP equal the number of frequent customers and their preference for MBPP,respectively,we show that compared with the MBPP,employing the TBPP is beneficial for the platform but is detrimental for customers and providers.However,adopting the MBPP(TBPP)can simultaneously benefit the platform,customers and providers if frequent customers'preference for MBPP is higher(lower)than regular customers'preference for TBPP or the number of frequent customers is larger(less)than regular customers.展开更多
Type of Company： Government institution. New Preparartions and Late-Model Drug Delivery System Technical Plaform of Peking University School of Pharmaceutical Sciences is a national technical plaform for developing n...Type of Company： Government institution. New Preparartions and Late-Model Drug Delivery System Technical Plaform of Peking University School of Pharmaceutical Sciences is a national technical plaform for developing new and important drugs. The person in charge for the platform is a pharmaceutical science professor of Peking University School of Pharmaceutical Sciences. The plaform selects the following as the main research areas： late-model carrier drug delivery system, biotechnological drug delivery system,展开更多
The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored.Compared with conventional treatments,small nucleic acid therapeutics have the potential to achieve long...The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored.Compared with conventional treatments,small nucleic acid therapeutics have the potential to achieve long-lasting or even curative effects via gene editing.As a result of recent technological advances,effcient small nucleic acid delivery for therapeutic and biomedical applications has been achieved,accelerating their clinical translation.Here,we review the increasing number of small nucleic acid therapeutic classes and the most common chemical modifications and delivery platforms.We also discuss the key advances in the design,development and therapeutic application of each delivery platform.Furthermore,this review presents comprehensive profiles of currently approved small nucleic acid drugs,including 11 antisense oligonucleotides(AsOs),2 aptamers and 6 siRNA drugs,summarizing their modifications,disease-specific mechanisms of action and delivery strategies.Other candidates whose clinical trial status has been recorded and updated are also discussed.We also consider strategic issues such as important safety considerations,novel vectors and hurdles for translating academic breakthroughs to the clinic.Small nucleic acid therapeutics have produced favorable results in clinical trials and have the potential to address previously"undruggable"targets,suggesting that they could be useful for guiding the development of additional clinical candidates.展开更多
China's top delivery platforms are slashing beverage prices in a battle for users.But are deep discounts enough to reshape a deeply entrenched market?Zhou Ying used to brew her own coffee at home to save money.Now...China's top delivery platforms are slashing beverage prices in a battle for users.But are deep discounts enough to reshape a deeply entrenched market?Zhou Ying used to brew her own coffee at home to save money.Now she orders her morning cup.展开更多
Diabetes,characterized by hyperglycemia,is a major cause of death and disability worldwide.Peptides,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ...Diabetes,characterized by hyperglycemia,is a major cause of death and disability worldwide.Peptides,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body.Compared to subcutaneous injection,oral administration of anti-diabetic peptides is a preferred approach.However,biological barriers significantly reduce the efficacy of oral peptide therapeutics.Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes.This review will highlight(1)the benefits of oral anti-diabetic peptide therapeutics;(2)the biological barriers for oral peptide delivery,including pH and enzyme degradation,intestinal mucosa barrier,and biodistribution barrier;(3)the delivery platforms to overcome these biological barriers.Additionally,the review will discuss the prospects in this field.The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.展开更多
Despite noteworthy technological progress and promising preclinical trials,brain disorders are still the leading causes of death globally.Extracellular vesicles(EVs),nano-/micro-sized membrane vesicles carrying bioact...Despite noteworthy technological progress and promising preclinical trials,brain disorders are still the leading causes of death globally.Extracellular vesicles(EVs),nano-/micro-sized membrane vesicles carrying bioactive molecules,are involved in cellular communication.Based on their unique properties,including superior biocompatibility,non-immunogenicity,and blood-brain barrier(BBB)penetration,EVs can shield their cargos from immune clearance and transport them to specific site,which have attracted increasing interests as novel nanocarriers for brain disorders.However,considering the limitations of native EVs,such as poor encapsulation efficiency,inadequate targeting capability,uncontrolled drug release,and limited production,researchers bioengineer EVs to fully exploit the clinical potential.Herein,this review initially describes the basic properties,biogenesis,and uptake process of EVs from different subtypes.Then,we highlight the application of EVs derived from different sources for personalized therapy and novel strategies to construct bioengineered EVs for enhanced diagnosis and treatment of brain disorders.Besides,it also presents a systematic comparison between EVs and other brain-targeted nanocarriers.Finally,existing challenges and future perspectives of EVs have been discussed,hoping to bolster the research from benchtop to bedside.展开更多
Oncolytic virus(OV)therapy has been shown to be an effective targeted cancer therapy treatment in recent years,providing an avenue of treatment that poses no damage to surrounding healthy tissues.Not only do OVs cause...Oncolytic virus(OV)therapy has been shown to be an effective targeted cancer therapy treatment in recent years,providing an avenue of treatment that poses no damage to surrounding healthy tissues.Not only do OVs cause direct oncolysis,but they also amplify both innate and adaptive immune responses generating long-term anti-tumour immunity.Genetically engineered OVs have become the common promising strategy to enhance anti-tumour immunity,safety,and efficacy as well as targeted delivery.The studies of various OVs have been accomplished through phase I-III clinical trial studies.In addition,the uses of carrier platforms of organic materials such as polymer chains,liposomes,hydrogels,and cell carriers have played a vital role in the potentially targeted delivery of OVs.The mechanism,rational design,recent clinical trials,applications,and the development of targeted delivery platforms of OVs will be discussed in this review.展开更多
基金by the National Natural Science Foundation of China[grant numbers 82170459,2021]Sichuan Science and Technology Program[grant numbers 2022YFH0007,2022]+2 种基金Sichuan Science and Technology Program[grant numbers 23NSFSC1345,2022]the Key Project of Application and Basic Research of Southwest Medical University[grant numbers 2021ZKZD016,2021]the Special Support Project for Young Talents of Southwest Medical University[grant numbers 2020-2022].
文摘In the inflammatory microenvironment,there are numerous exosomes secreted by immune cells(Macrophages,neutrophils,dendritic cells),mesenchymal stem cells(MSCs)and platelets as intercellular communicators,which participate in the regulation of inflammation by modulating gene expression and releasing anti-inflammatory factors.Due to their good biocompatibility,accurate targeting,low toxicity and immunogenicity,these exosomes are able to selectively deliver therapeutic drugs to the site of inflammation through interactions between their surface-antibody or modified ligand with cell surface receptors.Therefore,the role of exosome-based biomimetic delivery strategies in inflammatory diseases has attracted increasing attention.Here we review current knowledge and techniques for exosome identification,isolation,modification and drug loading.More importantly,we highlight progress in using exosomes to treat chronic inflammatory diseases such as rheumatoid arthritis(RA),osteoarthritis(OA),atherosclerosis(AS),and inflammatory bowel disease(IBD).Finally,we also discuss their potential and challenges as anti-inflammatory drug carriers.
文摘Online Food Delivery Platforms(OFDPs)has witnessed phenomenal growth in the past few years,especially this year due to the COVID-19 pandemic.This Pandemic has forced many governments across the world to give momentum to OFD services and make their presence among the customers.The Presence of several multinational and national companies in this sector has enhanced the competition and companies are trying to adapt various marketing strategies and exploring the brand experience(BEX)dimension that helps in enhancing the brand equity(BE)of OFDPs.BEXs are critical for building brand loyalty(BL)and making companies profitable.Customers can experience different kinds of brand experiences through feeling,emotions,affection,behavior,and intellect.The present research work is taken up to analyze the factors affecting BEX and its impact on BL and BE of the OFDPs and analyze the mediating role of BL in the relationship between BEX and BE of the OFDPs in the Indian context.A survey of 457 Indian customers was carried out.A questionnaire was used for data collection and a mediation study was used to test hypothesized relationships.Our computational analysis reveals that BEX influences the BL and BE of OFDPs.The study further indicates that BL mediates the relationship between BEX and BE of OFDPs.The effective marketing and relationship management practices will help company to enhance BEX that will enable in enhancing BL and raising BE of their product.It therefore provides a more thorough analysis of BEX constructs and their consequences than previous research.Some of the managerial implication,limitations,and scope of future research are also presented in the study.
文摘Oracle and ZTE announced on April 21, 2008 that they have extended their alliance in connection with the marketing and development of Service Delivery Platform offerings in China and globally.
基金supported by the Natural Science Foundation of China(No.82073311)Science&Technology Department of Sichuan Province Individualized Drug Therapy Small Molecule Innovative Drugs Sichuan Youth Science and Technology Innovation Research Team(No.2022JDTD0025)Sichuan Traditional Chinese Medicine Administration(No.2023MS026).
文摘The successful approval of peptide-based drugs can be attributed to a collaborative effort across multiple disciplines.The integration of novel drug design and synthesis techniques,display library technology,delivery systems,bioengineering advancements,and artificial intelligence have significantly expedited the development of groundbreaking peptide-based drugs,effectively addressing the obstacles associated with their character,such as the rapid clearance and degradation,necessitating subcutaneous injection leading to increasing patient discomfort,and ultimately advancing translational research efforts.Peptides are presently employed in the management and diagnosis of a diverse array of medical conditions,such as diabetes mellitus,weight loss,oncology,and rare diseases,and are additionally garnering interest in facilitating targeted drug delivery platforms and the advancement of peptide-based vaccines.This paper provides an overview of the present market and clinical trial progress of peptide-based therapeutics,delivery platforms,and vaccines.It examines the key areas of research in peptide-based drug development through a literature analysis and emphasizes the structural modification principles of peptide-based drugs,as well as the recent advancements in screening,design,and delivery technologies.The accelerated advancement in the development of novel peptide-based therapeutics,including peptide-drug complexes,new peptide-based vaccines,and innovative peptide-based diagnostic reagents,has the potential to promote the era of precise customization of disease therapeutic schedule.
基金the National Natural Science Foundation of China(NSFC,22367022)。
文摘Drug distribution in cells depends on the partition nature determined by its chemical structure,which could influence drug concentration and efficacy.Conversely,precise delivery of a drug to the specific condensates in cells,such as organelles,means a distinct way to remodel the drug action.We here introduce an unprecedented molecular delivery platform with an accurate loading capacity of a drug,able to simultaneously target mitochondria(Mito)and endoplasmic reticulum(ER)while releasing the parent drug in situ.For our proof of concept,we used desloratadine(Des),a common anti-allergic drug,as the parent drug to develop a delivery platform(DDY)for chemotherapy.DDY can respond to the glutathione(GSH)levels,allowing for the selective release of Des in Mito and ER in cancer cells,which have higher GSH concentrations than normal cells.The release of Des in Mito and ER effectively and selectively induces tumor cells to ferroptosis while causing minimal toxicity to normal cells.DDY exhibits a satisfied chemotherapy efficacy in xenograft and metastasis cancer models,which should originate from the effects of Des in the two organelles.The result demonstrates the potential for developing chemotherapy from a currently approved drug with little anti-cancer activity through a precise distribution of it to organelles,significantly broadening the space of drug candidates for future chemotherapy.
基金Key R&D plan of the Ministry of Science and Technology,Grant/Award Number:2023YFC2505900National Natural Science Foundation of China,Grant/Award Numbers:82172837,82071799,81972683。
文摘Exosomes,a specific subset of extracellular vesicles,have diverse functions in various biological processes.In the field of cancer research,there has been a growing interest in the potential of exosomes to act as versatile vehicles for targeted tumor imaging and therapy.In this study,we constructed a targeted delivery platform using hypoimmunogenic exosomes by genetically modifyingβ2-microglobulin knocking-out HEK-293F cells to express a fusion protein,referred to asαMUC1-Exo,which comprises the exosomal membrane-enriched platelet-derived growth factor receptor,intracellular nanoluciferase,and extracellular anti-MUC1 single-chain variable fragment.The findings of this study indicate thatαMUC1-Exos exhibited notable drug delivery properties toward MUC1-positive pancreatic cancer cells,resulting in a substantial inhibition of tumor growth.Moreover,these exosomes demon-strated a high level of biosafety and the absence of any adverse effects.The application of engineered exosomes as a vehicle for drug delivery holds promise for enhancing the immunogenicity of neoplastic cells following treatment,thereby inducing antitumor immune memory in mice with intact immune systems,and also improving the response to anti-PD1 therapy.This approach utilizing engineered exosomes for Gemcitabine administration holds promise as a potential strategy for overcoming drug resistance in pancreatic carcinoma thereby improving the overall treatment efficacy.
基金the National Natural Science Foundation of China(82125037,82274104,82074024,82374042)National Key R&D Program of China(2023YFC2308200)+3 种基金Jiangsu Provincial Medical Innovation Center(CXZX202225)the Natural Science Foundation of Jiangsu Province(BK20240144)the Innovation Projects of State Key Laboratory on Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture(NZYSKL240103)Nanjing University of Chinese Medicine’s Project(RC202407).
文摘Plant-derived nanovesicles(PDNVs),including plant extracellular vesicles(EVs)and plant exosome-like nanovesicles(ELNs),are natural nano-sized membranous vesicles containing bioactive molecules.PDNVs consist of a bilayer of lipids that can effectively encapsulate hydrophilic and lipophilic drugs,improving drug stability and solubility as well as providing increased bioavailability,reduced systemic toxicity,and enhanced target accumulation.Bioengineering strategies can also be exploited to modify the PDNVs to achieve precise targeting,controlled drug release,and massive production.Meanwhile,they are capable of crossing the blood-brain barrier(BBB)to transport the cargo to the lesion sites without harboring human pathogens,making them excellent therapeutic agents and drug delivery nanoplatform candidates for brain diseases.Herein,this article provides an initial exposition on the fundamental characteristics of PDNVs,including biogenesis,uptake process,isolation,purification,characterization methods,and source.Additionally,it sheds light on the investigation of PDNVs’utilization in brain diseases while also presenting novel perspectives on the obstacles and clinical advancements associated with PDNVs.
基金Xiaogang Lin is the corresponding author.We thank the Editor(s)and two anonymous referees for their constructive and insightful comments,which help us significantly improve the quality of our paper.This paper was supported by the National Natural Science Foundation of China under Grant No.72001048.
文摘In recent years,two pricing policies are commonly adopted by on-demand delivery service platforms(e.g,Meituan PaoTui and Costco)that provide delivery services to heterogeneous customers via self-scheduling providers.One called"transaction-based"pricing policy(TBPP)allows the platforms to determine a per-service wage paid to providers and a price charged to customers for each transaction.The other one called"membership-based"pricing policy(MBPP)also allows the platforms to announce a wage paid to providers but charge customers a membership fee for using an unlimited number of the services in a certain period(e.g.,one month).This paper considers an on-demand delivery service platform with self-scheduling providers and two classes of customers(i.e.,regular and frequent customers).We aim to analyze and compare the platform's profits and welfare performances generated by the two pricing policies.If the number of regular customers and their preference for TBPP equal the number of frequent customers and their preference for MBPP,respectively,we show that compared with the MBPP,employing the TBPP is beneficial for the platform but is detrimental for customers and providers.However,adopting the MBPP(TBPP)can simultaneously benefit the platform,customers and providers if frequent customers'preference for MBPP is higher(lower)than regular customers'preference for TBPP or the number of frequent customers is larger(less)than regular customers.
文摘Type of Company： Government institution. New Preparartions and Late-Model Drug Delivery System Technical Plaform of Peking University School of Pharmaceutical Sciences is a national technical plaform for developing new and important drugs. The person in charge for the platform is a pharmaceutical science professor of Peking University School of Pharmaceutical Sciences. The plaform selects the following as the main research areas： late-model carrier drug delivery system, biotechnological drug delivery system,
基金supported by the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYGD23008)by the Frontiers Medical Center,Tianfu Jincheng Laboratory Foundation(No.TFJC202310005)by the Scientific Research and Innovation Team Program of Sichuan University of Science and Technology(No.SUSE652B003).
文摘The ability of small nucleic acids to modulate gene expression via a range of processes has been widely explored.Compared with conventional treatments,small nucleic acid therapeutics have the potential to achieve long-lasting or even curative effects via gene editing.As a result of recent technological advances,effcient small nucleic acid delivery for therapeutic and biomedical applications has been achieved,accelerating their clinical translation.Here,we review the increasing number of small nucleic acid therapeutic classes and the most common chemical modifications and delivery platforms.We also discuss the key advances in the design,development and therapeutic application of each delivery platform.Furthermore,this review presents comprehensive profiles of currently approved small nucleic acid drugs,including 11 antisense oligonucleotides(AsOs),2 aptamers and 6 siRNA drugs,summarizing their modifications,disease-specific mechanisms of action and delivery strategies.Other candidates whose clinical trial status has been recorded and updated are also discussed.We also consider strategic issues such as important safety considerations,novel vectors and hurdles for translating academic breakthroughs to the clinic.Small nucleic acid therapeutics have produced favorable results in clinical trials and have the potential to address previously"undruggable"targets,suggesting that they could be useful for guiding the development of additional clinical candidates.
文摘China's top delivery platforms are slashing beverage prices in a battle for users.But are deep discounts enough to reshape a deeply entrenched market?Zhou Ying used to brew her own coffee at home to save money.Now she orders her morning cup.
基金This study was supported by the National Science Fund of Distinguished Young Scholars(No.82025032,China)the National Natural Science Foundation of China(No.82073773,China)+1 种基金the Key Research Program of Chinese Academy of Sciences(ZDBS-ZRKJZ-TLC005,China)Young Elite Scientists Sponsorship Program by CAST(No.2022QNRC001,China).
文摘Diabetes,characterized by hyperglycemia,is a major cause of death and disability worldwide.Peptides,such as insulin and glucagon-like peptide-1(GLP-1)analogs,have shown promise as treatments for diabetes due to their ability to mimic or enhance insulin's actions in the body.Compared to subcutaneous injection,oral administration of anti-diabetic peptides is a preferred approach.However,biological barriers significantly reduce the efficacy of oral peptide therapeutics.Recent advancements in drug delivery systems and formulation techniques have greatly improved the oral delivery of peptide therapeutics and their efficacy in treating diabetes.This review will highlight(1)the benefits of oral anti-diabetic peptide therapeutics;(2)the biological barriers for oral peptide delivery,including pH and enzyme degradation,intestinal mucosa barrier,and biodistribution barrier;(3)the delivery platforms to overcome these biological barriers.Additionally,the review will discuss the prospects in this field.The information provided in this review will serve as a valuable guide for future developments in oral anti-diabetic peptide therapeutics.
基金support from National Natural Science Foundation of China(Nos.82274104,81903557,and 82074024)Natural Science Foundation of Jiangsu Province(No.BK20190802)+3 种基金Young Elite Scientists Sponsorship Program by CACM(No.2021-QNRC2-A01)Natural Science Foundation Youth Project of Nanjing University of Chinese Medicine(No.NZY81903557)College Students’Innovative Entrepreneurial Training of Jiangsu Province(No.202110315021)College Students’Innovative Entrepreneurial Training of Kangyuan School of Chinese Herbal Medicine of Nanjing University of Chinese Medicine(No.kyxysc12).
文摘Despite noteworthy technological progress and promising preclinical trials,brain disorders are still the leading causes of death globally.Extracellular vesicles(EVs),nano-/micro-sized membrane vesicles carrying bioactive molecules,are involved in cellular communication.Based on their unique properties,including superior biocompatibility,non-immunogenicity,and blood-brain barrier(BBB)penetration,EVs can shield their cargos from immune clearance and transport them to specific site,which have attracted increasing interests as novel nanocarriers for brain disorders.However,considering the limitations of native EVs,such as poor encapsulation efficiency,inadequate targeting capability,uncontrolled drug release,and limited production,researchers bioengineer EVs to fully exploit the clinical potential.Herein,this review initially describes the basic properties,biogenesis,and uptake process of EVs from different subtypes.Then,we highlight the application of EVs derived from different sources for personalized therapy and novel strategies to construct bioengineered EVs for enhanced diagnosis and treatment of brain disorders.Besides,it also presents a systematic comparison between EVs and other brain-targeted nanocarriers.Finally,existing challenges and future perspectives of EVs have been discussed,hoping to bolster the research from benchtop to bedside.
基金The work was financial supported by the National Science Foundation and South Carolina Experimental Program to Stimulate Competitive Research and Institutional Development Awards(SC EPSCoR IDeA)program under NSF Award.
文摘Oncolytic virus(OV)therapy has been shown to be an effective targeted cancer therapy treatment in recent years,providing an avenue of treatment that poses no damage to surrounding healthy tissues.Not only do OVs cause direct oncolysis,but they also amplify both innate and adaptive immune responses generating long-term anti-tumour immunity.Genetically engineered OVs have become the common promising strategy to enhance anti-tumour immunity,safety,and efficacy as well as targeted delivery.The studies of various OVs have been accomplished through phase I-III clinical trial studies.In addition,the uses of carrier platforms of organic materials such as polymer chains,liposomes,hydrogels,and cell carriers have played a vital role in the potentially targeted delivery of OVs.The mechanism,rational design,recent clinical trials,applications,and the development of targeted delivery platforms of OVs will be discussed in this review.
