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

详细信息    查看全文

• 作者：Sohee Son ; Seungyong Song ; So Jin Lee ; Solki Min ; Sun Ah Kim ; Ji Young Yhee ; Myung Sook Huh ; Ick Chan Kwon ; Seo Young Jeong ; Youngro Byun ; Sun Hwa Kim ; Kwangmeyung Kim
• 关键词：Cancer therapy ; RNAi ; Polymerized siRNA ; Protein based carrier ; Human serum albumin
• 刊名：Biomaterials
• 出版年：2013
• 出版时间：December, 2013
• 年：2013
• 卷：34
• 期：37
• 页码：9475-9485
• 全文大小：3481 K

文摘

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.