Raloxifene-loaded and aptamer-bonded exosomes induce autophagic and apoptotic death in HeLa cells by enhancing the lysosomotropic effect  

作　　者：OMER ERDOGAN GULEN MELIKE DEMIRBOLAT OZGE CEVIK 

机构地区：[1]Department of Medical Biochemistry,School of Medicine,Aydin Adnan Menderes University,Aydin,09010,Turkey [2]Department of Pharmaceutical Technology,Faculty of Pharmacy,Acibadem Mehmet Ali Aydinlar University,Istanbul,34758,Turkey

出　　处：《BIOCELL》2023年第5期1051-1063,共13页生物细胞（英文）

基　　金：supported by a Grant(221S945)from the Scientific and Technological Research Council of Turkey(TUBITAK);an Aydin Adnan Menderes University Research Grant(ADU-TPF-20041).

摘　　要：Background:Raloxifene,a selective estrogen receptor modulator,is also known to be a lysosomotropic agent.The bioavailability of raloxifene is around 2%due to extensive hepatic transport.Exosomes are nanosized vesicles that are naturally released from cells.Method:In this study,exosomes released from HeLa cervical cancer cells were loaded with raloxifene to increase its bioavailability,and an aptamer was attached to the exosome membrane for targeting only HeLa cells.Characterization of exosomes isolated from HeLa cells was performed by transmission electron microscopy,zeta sizer,and western blotting.In addition,the cytotoxic,apoptotic,autophagic,and lysosomotropic effects of the prepared Exo-Apt-Ral formulation on HeLa cervical cancer cells were investigated.Results:According to zeta analysis,the sizes of the empty exosome and Exo-Apt-Ral formulation were measured as 66±12 and 120±21 nm,respectively.There was a rise in the lysosomal permeability of HeLa cells after the Exo-Apt-Ral application.In addition,both apoptotic and autophagic death mechanisms were triggered in HeLa cells after the Exo-Apt-Ral application.Conclusion:This study showed that raloxifene functionalized by loading into aptamer-bound exosomes can be a new targeted drug carrier system for cervical cancer.

关 键 词：APTAMER Autophagy Cervical cancer EXOSOMES RALOXIFENE 

分 类 号：R73[医药卫生—肿瘤] R96[医药卫生—临床医学]