Son, Sohee Song, Seungyong Lee, So Jin Min, Solki Kim, Sun Ah Yhee, Ji Young Huh, Myung Sook Kwon, Ick Chan Jeong, Seo Young Byun, Youngro Kim, Sun Hwa Kim, Kwangmeyung 2024-01-20T11:02:20Z 2024-01-20T11:02:20Z 2021-09-05 2013-12 0142-9612 https://pubs.kist.re.kr/handle/201004/127396 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 (TM)-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. (C) 2013 Elsevier Ltd. All rights reserved. English ELSEVIER SCI LTD CONTROLLED-RELEASE RNA INTERFERENCE GENE NANOPARTICLES STABILITY ACID Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors Article 10.1016/j.biomaterials.2013.08.085 1 BIOMATERIALS, v.34, no.37, pp.9475 - 9485 BIOMATERIALS 34 37 9475 9485 scie scopus 000326901200024 2-s2.0-84884814016 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article CONTROLLED-RELEASE RNA INTERFERENCE GENE NANOPARTICLES STABILITY ACID Cancer therapy RNAi Polymerized siRNA Protein based carrier Human serum albumin