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

Paper ID Volume ID Publish Year Pages File Format Full-Text
6457 491 2013 11 PDF Available
Title
Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors
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.

Keywords
Cancer therapy; RNAi; Polymerized siRNA; Protein based carrier; Human serum albumin
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Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 37, December 2013, Pages 9475–9485
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us