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

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

Research output: Contribution to journalArticle

45 Citations (Scopus)

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 invitro 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.

Original languageEnglish
Pages (from-to)9475-9485
Number of pages11
JournalBiomaterials
Volume34
Issue number37
DOIs
Publication statusPublished - 2013 Dec

Keywords

  • Cancer therapy
  • Human serum albumin
  • Polymerized siRNA
  • Protein based carrier
  • RNAi

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint Dive into the research topics of 'Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors'. Together they form a unique fingerprint.

  • Cite this

    Son, S., Song, S., Lee, S. J., Min, S., Kim, S. A., Yhee, J. Y., Huh, M. S., Chan Kwon, I., Jeong, S. Y., Byun, Y., Kim, S. H., & Kim, K. (2013). Self-crosslinked human serum albumin nanocarriers for systemic delivery of polymerized siRNA to tumors. Biomaterials, 34(37), 9475-9485. https://doi.org/10.1016/j.biomaterials.2013.08.085