Cell-penetrating peptide mimicking polymer-based combined delivery of paclitaxel and siRNA for enhanced tumor growth suppression

Title
Cell-penetrating peptide mimicking polymer-based combined delivery of paclitaxel and siRNA for enhanced tumor growth suppression
Authors
장연림Ui Jeong Yun이민상김명구손소희이규리채수영임동우김홍태김선화정지훈
Keywords
Biomimetic polymer; Combined delivery; siRNA; Anticancer drug; Combination cancer therapy
Issue Date
2012-09
Publisher
International journal of pharmaceutics
Citation
VOL 434, NO 1-2, 488-493
Abstract
Cancer chemotherapy is often limited, since more than one molecule is usually involved with the cancer pathogenesis. A combination of therapeutic drugs would be a promising approach to overcome the complexity of tumors. In this study, a conjugate (DA3) of deoxycholic acid and low molecular weight polyethylenimine (PEI 1.8 kDa), which has a property that mimics that of cell penetrating peptides (CPPs), was used for simultaneous delivery of an anticancer drug and siRNA. When complexed with siRNA, DA3 showed significantly higher target gene silencing efficiency than PEI 25 kDa. The gene silencing efficiency of DA3 was maintained even in the presence of endocytosis inhibitors, suggesting that the polymeric carrier can mediate an endocytosis-independent macromolecular transduction similar to CPPs. The capability of forming a micelle-like core–shell structure enables the conjugates to encapsulate and dissolve paclitaxel (PTX), a water-insoluble drug. The drug-loaded cationic micelles can then interact with siRNA to form stable complexes (PTX/DA3/siRNA). The PTX/DA3/siRNA showed significantly enhanced inhibition of cancer cell growth. When administered into tumor-bearing animals, the PTX/DA3/siRNA demonstrated significant suppression of tumor growth, providing potential usefulness in clinical settings.
URI
http://pubs.kist.re.kr/handle/201004/43966
ISSN
03785173
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KIST Publication > Article
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