Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors

Title
Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors
Authors
손소희송승용이소진Solki Min김선아이지영허명숙권익찬정서영변영로김선화김광명
Keywords
Cancer therapy; RNAi; Polymerized siRNA; Protein based carrier; Human serum albumin
Issue Date
2013-12
Publisher
Biomaterials
Citation
VOL 34, NO 37, 9475-9485
Abstract
The safe and effective systemic delivery of siRNA is a prerequisite for the successful development of siRNA-based cancer therapeutics. For the enhanced delivery of siRNA, cationic lipids and polymers have been widely used as siRNA carriers to form electrolyte complexes with anionic siRNA. However, the considerable toxicity of strong cationic-charged molecules hampers their clinical use. In this study, we utilized human serum albumin (HSA), which is the most abundant of the plasma proteins, as a siRNA carrier for systemic tumor-targeted siRNA delivery. Both HSA and siRNA molecules were thiol-introduced to improve the binding affinity for each other. The resulting thiolated HSA (tHSA) and polymerized siRNA (psi) formed stable nanosized complexes (psi–tHSAs) by chemical crosslinking and self-crosslinking. After internalization, the psi–tHSAs showed target gene silencing activity in vitro comparable to conventional Lipofectamine™-siRNA complexes, without remarkable cytotoxicity. After intravenous injection in tumor-bearing mice, psi–tHSAs accumulated specifically at the tumor sites, leading to efficient gene silencing in the tumors in a sequential manner. The therapeutic VEGF siRNA was loaded into psi–tHSAs, which significantly inhibited tumor-related angiogenesis in PC-3 tumor xenografts and resulted in retarding the growth of PC-3 tumors. The results showed that self-crosslinked psi–tHSA nanocarriers might provide a promising approach for the systemic siRNA therapy of various human cancers.
URI
http://pubs.kist.re.kr/handle/201004/46421
ISSN
01429612
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KIST Publication > Article
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