Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient ce...Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.展开更多
Extracellular vesicles(EVs)are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size:exosomes,microv...Extracellular vesicles(EVs)are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size:exosomes,microvesicles,and apoptotic bodies.Exosomes are the smallest(30–150 nm)of these EVs,and play an important role in EV-mediated cell-to-cell interactions,by transferring proteins,nucleic acids and,lipids from their parental cells to adjacent or distant cells to alter their phenotypes.Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer ofmRNAs and microRNAs to neighboring cells.However,exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues.Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms,including in targeted therapy approaches.This review will briefly summarize information on exosome membrane proteins components and their role in exosome–cell interactions,including proteins associated with specific cell-interactions and diseases,and the potential for using exosome membrane proteins in therapeutic targeting approaches.展开更多
基金supported by Tulane Weatherhead Endowment Fund (USA)
文摘Extracellular vesicles(EVs)are secreted by both eukaryotes and prokaryotes,and are present in all biological fluids of vertebrates,where they transfer DNA,RNA,proteins,lipids,and metabolites from donor to recipient cells in cell-to-cell communication.Some EV components can also indicate the type and biological status of their parent cells and serve as diagnostic targets for liquid biopsy.EVs can also natively carry or be modified to contain therapeutic agents(e.g.,nucleic acids,proteins,polysaccharides,and small molecules)by physical,chemical,or bioengineering strategies.Due to their excellent biocompatibility and stability,EVs are ideal nanocarriers for bioactive ingredients to induce signal transduction,immunoregulation,or other therapeutic effects,which can be targeted to specific cell types.Herein,we review EV classification,intercellular communication,isolation,and characterization strategies as they apply to EV therapeutics.This review focuses on recent advances in EV applications as therapeutic carriers from in vitro research towards in vivo animal models and early clinical applications,using representative examples in the fields of cancer chemotherapeutic drug,cancer vaccine,infectious disease vaccines,regenerative medicine and gene therapy.Finally,we discuss current challenges for EV therapeutics and their future development.
基金The work was partially supported by research funding provided by the National Institutes of Health(Grants No.U01CA214254,R01HD090927,R01AI122932,R01AI113725,and R21Al126361-01),and Arizona Biomedical Research Commission(ABRC)young investigator award.
文摘Extracellular vesicles(EVs)are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size:exosomes,microvesicles,and apoptotic bodies.Exosomes are the smallest(30–150 nm)of these EVs,and play an important role in EV-mediated cell-to-cell interactions,by transferring proteins,nucleic acids and,lipids from their parental cells to adjacent or distant cells to alter their phenotypes.Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer ofmRNAs and microRNAs to neighboring cells.However,exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues.Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms,including in targeted therapy approaches.This review will briefly summarize information on exosome membrane proteins components and their role in exosome–cell interactions,including proteins associated with specific cell-interactions and diseases,and the potential for using exosome membrane proteins in therapeutic targeting approaches.