细胞外囊泡的表面修饰及其在中药活性成分递送中的应用

邵钰柔; 王宇彤; 陈志鹏

细胞外囊泡的表面修饰及其在中药活性成分递送中的应用

南京中医药大学药学院，江苏南京 210023

计量
- 文章访问数: 805
- HTML全文浏览量: 31
- PDF下载量: 488
- 被引次数: 0
出版历程
- 刊出日期: 2020-07-10

Surface Modification Strategies of Extracellular Vesicles and Their Applications in Natural Products Delivery

摘要

摘要: 细胞外囊泡（Extracellular vesicles，EVs）是由细胞分泌的脂质囊泡，具有天然、稳定、生物相容性高等特点。近年来，EVs作为纳米仿生药物载体的报道逐渐增加，通过表面修饰技术获得功能化囊泡，进一步拓展了EVs的应用。中医药传承千年，疗效显著，但存在部分有效成分的水溶性差、生物利用度低、细胞毒性高等问题，利用EVs作为载体递送中药活性成分能够使药物的药效得到更好的发挥。该文介绍了EVs的种类、产生机制以及表面修饰方法，并总结了其作为中药活性成分载体的应用进展。
- 细胞外囊泡 /
- 外泌体 /
- 表面修饰 /
- 中药活性成分 /
- 药物递送系统
Abstract: Extracellular vesicles (EVs) are small membrane vesicles secreted from cells， possessing advantages of nature， high stability and favorable biocompatibility. Recently， EVs have been widely employed as biomimetic nano carriers in drug delivery， and surface modification extends their application. Chinese herbal medicines have been used for disease treatment over thousands of years， however， poor solubility， low bioavailability and high cytotoxicity of some of active ingredients limits their therapeutic effects. Therefore， using EVs as carriers of active ingredients in Chinese medicines for drug delivery is an efficient approach to enhance their bioavailability as well as the corresponding therapeutic efficiency. In this review， we summarize different types of EVs and their respective production process， present the surface modification methods to obtain functional EVs， and introduce some of their applications in natural products delivery.
- extracellular vesicles /
- exosomes /
- surface modification /
- active ingredients of traditional Chinese medicine /
- drug delivery system

HTML全文

参考文献(48)

[1]	KOWAL J，ARRAS G，COLOMBO M，et al．Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes[J]．Proc Natl Acad Sci USA，2016，113(8)：968-977．
[2]	WILLMS E，CABANAS C，MAGER I，et al．Extracellular vesicle heterogeneity：subpopulations，isolation techniques，and diverse functions in cancer progression[J]．Front Immunol，2018，9：738．
[3]	ALAVI M，HAMIDI M．Passive and active targeting in cancer therapy by liposomes and lipid nanoparticles[J]．Drug Metab Pers Ther，2019，34(1)：1-8.
[4]	VISSER JG，VAN STADEN ADP，SMITH C．Harnessing macrophages for controlled-release drug delivery：Lessons from microbes[J]．Front Pharmacol，2019，10：22．
[5]	LUAN X，SANSANAPHONGPRICHA K，MYERS I，et al．Engineering exosomes as refined biological nanoplatforms for drug delivery[J]．Acta Pharmacol Sin，2017，38(6)：754-763．
[6]	LI MY，JIANG M，MENG J，et al．Exosomes：Carriers of pro-fibrotic signals and therapeutic targets in fibrosis[J]．Curr Pharm Des，2019，25(42)：4496-4509.
[7]	GOH WJ，ZOU S，ONG WY，et al．Bioinspired cell-derived nanovesicles versus exosomes as drug delivery systems：A cost-effective alternative[J]．Sci Rep，2017，7(1)：14322．
[8]	GUDBERGSSON JM，JONSSON K，SIMONSEN JB，et al．Systematic review of targeted extracellular vesicles for drug delivery-considerations on methodological and biological heterogeneity[J]．J Control Release，2019，306：108-120．
[9]	FRIAND V，DAVID G，ZIMMERMANN P．Syntenin and syndecan in the biogenesis of exosomes[J]．Biol Cell，2015，107(10)：331-341．
[10]	KAJIMOTO T，OKADA T，MIYA S，et al．Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes[J]．Nat Commun，2013，4：2712．
[11]	TRICARICO C，CLANCY J，D'SOUZA-SCHOREY C．Biology and biogenesis of shed microvesicles[J]．Small GTPases，2017，8(4)：220-232．
[12]	LU M，HUANG Y．Bioinspired exosome-like therapeutics and delivery nanoplatforms[J]．Biomaterials，2020，242：119925．
[13]	JURJ A，ZANOAGA O，BRAICU C，et al．A comprehensive picture of extracellular vesicles and their contents．Molecular transfer to cancer cells[J]．Cancers，2020，12(2)：298．
[14]	KOOIJMANS SA，VADER P，VAN DOMMELEN SM，et al．Exosome mimetics：A novel class of drug delivery systems[J]．Int J Nanomedicine，2012，7：1525-1541．
[15]	QIAO L，HU SQ，HUANG K，et al．Tumor cell-derived exosomes home to their cells of origin and can be used as Trojan horses to deliver cancer drugs[J]．Theranostics，2020，10(8)：3474-3487．
[16]	VANDERGRIFF A，HUANG K，SHEN DL，et al．Targeting regenerative exosomes to myocardial infarction using cardiac homing peptide[J]．Theranostics，2018，8(7)：1869-1878．
[17]	ANTES TJ，MIDDLETON RC，LUTHER KM，et al．Targeting extracellular vesicles to injured tissue using membrane cloaking and surface display[J]．J Nanobiotechnol，2018，16(1)：61．
[18]	DELCAYRE A，ESTELLES A，SPERINDE J，et al．Exosome Display technology：Applications to the development of new diagnostics and therapeutics[J]．Blood Cells Mol Dis，2005，35(2)：158-168．
[19]	ARMSTRONG JP，HOLME MN，STEVENS MM．Re-engineering extracellular vesicles as smart nanoscale therapeutics[J]．ACS Nano，2017，11(1)：69-83．
[20]	DANG XT，ZENG XR．Targeted therapeutic delivery using engineered exosomes and its applications in cardiovascular diseases[J]．Gene，2016，575(2)：377-384．
[21]	ALVAREZ-ERVITI L，SEOW Y，YIN HF，et al．Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes[J]．Nat Biotechnol，2011，29(4)：341-345．
[22]	OHNO S，TAKANASHI M，SUDO K，et al．Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells[J]．Mol Ther，2013，21(1)：185-191．
[23]	WAN Y，WANG LX，ZHU CD，et al．Aptamer-conjugated extracellular nanovesicles for targeted drug delivery[J]．Cancer Res，2018，78(3)：798-808．
[24]	KOOIJMANS SAA，GITZ-FRANCOIS JJJM，SCHIFFELERS RM，et al．Recombinant phosphatidylserine-binding nanobodies for targeting of extracellular vesicles to tumor cells： A plug-and-play approach[J]．Nanoscale，2018，10(5)：2413-2426．
[25]	OTZEN DE，BLANS K，WANG HB，et al．Lactadherin binds to phosphatidylserine-containing vesicles in a two-step mechanism sensitive to vesicle size and composition[J]．Biochim Biophys Acta，2012，1818(4)：1019-1027．
[26]	OUYANG T，LIU XH，OUYANG HS，et al．Recent trends in click chemistry as a promising technology for virus-related research[J]．Virus Res，2018，256：21-28．
[27]	ZOU Y，ZHANG L，YANG L，et al．"Click" chemistry in polymeric scaffolds：Bioactive materials for tissue engineering[J]．J Control Release，2018，273：160-179．
[28]	SMYTH T，PETROVA K，PAYTON NM，et al．Surface functionalization of exosomes using click chemistry[J]．Bioconjug Chem，2014，25(10)：1777-1784．
[29]	SATO YT，UMEZAKI K，SAWADA S，et al．Engineering hybrid exosomes by membrane fusion with liposomes[J]．Sci Rep，2016，6：21933．
[30]	DEHAINI D，WEI XL，FANG RH，et al．Erythrocyte-platelet hybrid membrane coating for enhanced nanoparticle functionalization[J]．Adv Mater Weinheim，2017，29(16)：1606209.
[31]	HADLA M，PALAZZOLO S，CORONA G，et al．Exosomes increase the therapeutic index of doxorubicin in breast and ovarian cancer mouse models[J]．Nanomedicine，2016，11(18)：2431-2441．
[32]	CASCAO R，FONSECA JE，MOITA LF．Celastrol：A spectrum of treatment opportunities in chronic diseases[J]．Front Med (Lausanne)，2017，4：69．
[33]	HEWLINGS SJ，KALMAN DS．Curcumin： A review of its' effects on human health[J]．Foods，2017，6(10)：92．
[34]	SUN DM，ZHUANG XY，XIANG XY，et al．A novel nanoparticle drug delivery system：the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes[J]．Mol Ther，2010，18(9)：1606-1614．
[35]	TIAN T，ZHANG HX，HE CP，et al．Surface functionalized exosomes as targeted drug delivery vehicles for cerebral ischemia therapy[J]．Biomaterials，2018，150：137-149．
[36]	刘常园，汤静，赵立艳. 花青素的稳定性与功能研究进展[J]. 食品与营养科学， 2018， 7(1): 53-63.
[37]	MUNAGALA R，AQIL F，JEYABALAN J，et al．Exosomal formulation of anthocyanidins against multiple cancer types[J]．Cancer Lett，2017，393：94-102．
[38]	SOLETI R，ANDRIANTSITOHAINA R，MARTINEZ MC．Impact of polyphenols on extracellular vesicle levels and effects and their properties as tools for drug delivery for nutrition and health[J]．Arch Biochem Biophys，2018，644：57-63．
[39]	AQIL F，KAUSAR H，AGRAWAL AK，et al．Exosomal formulation enhances therapeutic response of celastrol against lung cancer[J]．Exp Mol Pathol，2016，101(1)：12-21．
[40]	LIU YP，ZHAO Y，WEI ZH，et al．Targeting thioredoxin system with an organosulfur compound，diallyl trisulfide (DATS)，attenuates progression and metastasis of triple-negative breast cancer (TNBC)[J]．Cell Physiol Biochem，2018，50(5)：1945-1963．
[41]	刘玉萍，傅荣萍，陈彦，等. 大蒜素二烯丙基三硫醚-外泌体抗小鼠黑色素瘤肺转移的作用[J].药学学报， 2019， 54(9): 1688-1694.
[42]	AGRAWAL AK，AQIL F，JEYABALAN J，et al．Milk-derived exosomes for oral delivery of paclitaxel[J]．Nanomed-Nanotechnol，2017，13(5)：1627-1636．
[43]	SALARPOUR S， PARDAKHTY A， AHMADI-ZEIDABADI M， et al. Exoxome-loaded Paclitaxel: preparation and toxicity evaluation on two glioblastoma cell lines [J]. Nanomed Res J， 2019， 4(4): 239-246.
[44]	KIM MS， HANEY MJ， ZHAO Y， et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells[J]. Nanomed-Nanotechnol， 2016， 12(3): 655-664.
[45]	VIGNARD V，LABBE M，MAREC N，et al．MicroRNAs in tumor exosomes drive immune escape in melanoma[J]．Cancer Immunol Res，2020，8(2)：255-267．
[46]	QIAN LR，DIMA DL，BERCE C，et al．Protein dysregulation in graft versus host disease[J]．Oncotarget，2018，9(1)：1483-1491．
[47]	LENER T，GIMONA M，AIGNER L，et al．Applying extracellular vesicles based therapeutics in clinical trials - an ISEV position paper[J]．J Extracell Vesicles，2015，4：30087．
[48]	INGATO D，LEE JU，SIM SJ，et al．Good things come in small packages：Overcoming challenges to harness extracellular vesicles for therapeutic delivery[J]．J Control Release，2016，241：174-185．