Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs ...Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs are now approved for market by US Food and Drug Administration(FDA),and in the last two years,the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer,coronavirus disease 2019(COVID-19),metabolic diseases,and so on.The therapeutic benefits of PDCs are significant,but poor stability,low bioactivity,long research and development time,and slow clinical development process as therapeutic agents of PDC,how can we design PDCs more effectively and what is the future direction of PDCs?This review summarises the components and functions of PDCs for therapeutic,from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability,targeting,and stability of the various components of PDCs.This holds great promise for the future of PDCs,such as bicyclic peptide-toxin coupling or supramolecular nanostructures for peptide-conjugated drugs.The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised.The way is shown for future PDC development.展开更多
Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics.Mult...Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics.Multidrug resistance(MDR)in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure.There have been successes in the development of cancer nanomedicine to overcome MDR;however,relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer.This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells.Here,we discuss the advances,types of nanomedicines,and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.展开更多
生物药剂学分类系统(biopharmaceutics classification system,BCS)中的渗透性评价主要指向肠吸收问题,相对于单一成分药物,在中药生物药剂学分类系统(biopharmaceutics classification system of Chinese materia medica,CMMBCS)构建中...生物药剂学分类系统(biopharmaceutics classification system,BCS)中的渗透性评价主要指向肠吸收问题,相对于单一成分药物,在中药生物药剂学分类系统(biopharmaceutics classification system of Chinese materia medica,CMMBCS)构建中,多成分环境下的某单一成分吸收代谢受到多成分体系的影响而更为复杂,亟需适当的数学模型进行描述。作者团队在借鉴已有单成分肠吸收代谢数学算法的基础上,设计了多成分药物肠吸收代谢数学算法,提出参数P影响(多成分环境下某一单成分的吸收代谢相对于其单成分环境下的吸收代谢相对变化率)来反映多成分体系对其中某一单成分的吸收代谢影响,突出了多成分环境下药物肠吸收代谢的特点,为中药生物药剂学分类系统的构建奠定基础。展开更多
Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular dr...Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.展开更多
Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic sid...Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects.In the past decade,nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention,high accumulation at tumor sites,co-loading with different drugs,and combination of various therapies.This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy,radiotherapy,phototherapy(photothermal therapy and photodynamic therapy),chemodynamic therapy,gas therapy,and immunotherapy.Additionally,the therapeutic mechanisms,limitations,improvements,and future of the above therapies are discussed.展开更多
基金supported by the National Natural Science Foundation of China(NSFC,No.82073884,China)NSFC-Liaoning joint fund key program(No.U20A20413,China)+1 种基金Postdoctoral Research Startup Project(No.3110211220,China)Postdoctoral Research Startup Project(No.3110210640,China)。
文摘Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs are now approved for market by US Food and Drug Administration(FDA),and in the last two years,the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer,coronavirus disease 2019(COVID-19),metabolic diseases,and so on.The therapeutic benefits of PDCs are significant,but poor stability,low bioactivity,long research and development time,and slow clinical development process as therapeutic agents of PDC,how can we design PDCs more effectively and what is the future direction of PDCs?This review summarises the components and functions of PDCs for therapeutic,from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability,targeting,and stability of the various components of PDCs.This holds great promise for the future of PDCs,such as bicyclic peptide-toxin coupling or supramolecular nanostructures for peptide-conjugated drugs.The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised.The way is shown for future PDC development.
文摘Cancer nanomedicine is defined as the application of nanotechnology and nanomaterials for the formulation of cancer therapeutics that can overcome the impediments and restrictions of traditional chemotherapeutics.Multidrug resistance(MDR)in cancer cells can be defined as a decrease or abrogation in the efficacy of anticancer drugs that have different molecular structures and mechanisms of action and is one of the primary causes of therapeutic failure.There have been successes in the development of cancer nanomedicine to overcome MDR;however,relatively few of these formulations have been approved by the United States Food and Drug Administration for the treatment of cancer.This is primarily due to the paucity of knowledge about nanotechnology and the fundamental biology of cancer cells.Here,we discuss the advances,types of nanomedicines,and the challenges regarding the translation of in vitro to in vivo results and their relevance to effective therapies.
文摘生物药剂学分类系统(biopharmaceutics classification system,BCS)中的渗透性评价主要指向肠吸收问题,相对于单一成分药物,在中药生物药剂学分类系统(biopharmaceutics classification system of Chinese materia medica,CMMBCS)构建中,多成分环境下的某单一成分吸收代谢受到多成分体系的影响而更为复杂,亟需适当的数学模型进行描述。作者团队在借鉴已有单成分肠吸收代谢数学算法的基础上,设计了多成分药物肠吸收代谢数学算法,提出参数P影响(多成分环境下某一单成分的吸收代谢相对于其单成分环境下的吸收代谢相对变化率)来反映多成分体系对其中某一单成分的吸收代谢影响,突出了多成分环境下药物肠吸收代谢的特点,为中药生物药剂学分类系统的构建奠定基础。
基金supported by the National Key S&T Special Projects(No.2018ZX09201018-024)Sichuan Province Science and Technology Plan(2019YFH0115).
文摘Ocular drug delivery remains a significant challenge that is limited by poor corneal retention and permeation,resulting in low ocular bioavailability(<5%).Worse still,the most convenient and safe route of ocular drug administration,topical administration results in a drug bioavailability of less than 1%.iRGD modified drug delivery strategies have been developed for cancer therapy,however active targeting iRGD platforms for ocular drug delivery have yet to be explored.Herein,an iRGD modified liposomes was developed for ocular drug delivery via topical administration.The results indicated that iRGD modified liposomes could prolong the corneal retention time and enhance corneal permeability in an iRGD receptor mediated manner.These findings provided a novel strategy for topical ocular drug delivery for the treatment of posterior ocular diseases.
基金the Joint Fund Project of National Natural Science Foundation of China,No.U21A20309the National Natural Science Foundation of China,No.22078280,21776238,22006128,22108235 and 22208282.
文摘Colon cancer has attracted much attention due to its annually increasing incidence.Conventional chemotherapeutic drugs are unsatisfactory in clinical application because of their lack of targeting and severe toxic side effects.In the past decade,nanomedicines with multimodal therapeutic strategies have shown potential for colon cancer because of their enhanced permeability and retention,high accumulation at tumor sites,co-loading with different drugs,and combination of various therapies.This review summarizes the advances in research on various nanomedicine-based therapeutic strategies including chemotherapy,radiotherapy,phototherapy(photothermal therapy and photodynamic therapy),chemodynamic therapy,gas therapy,and immunotherapy.Additionally,the therapeutic mechanisms,limitations,improvements,and future of the above therapies are discussed.
