Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 7, Issue -, Pages 3823-3835Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S29328
Keywords
codelivery; gene silencing; chemotherapy; apoptosis; tumor targeting
Funding
- National Natural Science Foundation of China [50830107, 20974129, U1032002, 81070349, 81071167]
- Natural Science Foundation [9351027501000003]
- S&T Programs of Guangdong Province [2009B030803003, 2010B031500011]
- Guangzhou Scientific Project [2008Z1-D171]
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A folate conjugated ternary copolymer, FA-PEG-PEI-PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(epsilon-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.
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