Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin.
A folate conjugated ternary copolymer, FA-PEG-PEI-PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ɛ-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.
Center of Biomedical Engineering, Zhongshan School of Medicine, Guangzhou Medical University, Guangzhou, China.
Seyin
S
Zou
Nuo
N
Cao
Du
D
Cheng
Rongqin
R
Zheng
Jin
J
Wang
Kangshun
K
Zhu
Xintao
X
Shuai
D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D020868:Gene Silencing / Q000187:drug effects; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry / Q000493:pharmacokinetics; D011094:Polyethyleneimine / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; C494826:BAX protein, human; D004337:Drug Carriers; D011091:Polyesters; D034741:RNA, Small Interfering; D051028:bcl-2-Associated X Protein; C576039:polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol); D004317:Doxorubicin; D011094:Polyethyleneimine; D005492:Folic Acid