Hyaluronic acid receptor-targetable imidazolized nanovectors for induction of gastric cancer cell death by RNA interference

Eunjung Kim, Jaemoon Yang, Hyun Ouk Kim, Yonghee An, Eun Kyung Lim, Gyudo Lee, Taeyun Kwon, Jae Ho Cheong, Jin Suck Suh, Yong Min Huh, Seungjoo Haam

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)

Abstract

We have developed a nanovector consisting of hyaluronic acid (HA) and poly- l-lysine- graft-imidazole (PLI)-based polyplexes containing Bcl-xL-specific shRNA-encoding plasmid DNA (HA/PLI/pDNA) for CD44 targeted gastric cancer therapy. The prepared ternary polyplexes have a negative surface charge of -24 mV and a size of approximately 100 nm at an N/P ratio of 5 with HA/PLI molar ratio of 0.03. Gel electrophoresis and cell viability experiments demonstrated that the ternary polyplexes showed high stability and no cytotoxicity due to the anchored HA molecules on the surface of PLI/pDNA binary polyplexes. Selective cancer cell death was achieved by CD44-mediated gene delivery and the internalized gene was effectively escaped from endosomes due to the buffering capacity of imidazole groups in an acidic environment. These nanovectors may be highly efficient gene delivery tools that allow the selective destruction of metastatic gastric cancer cells.

Original languageEnglish
Pages (from-to)4327-4338
Number of pages12
JournalBiomaterials
Volume34
Issue number17
DOIs
Publication statusPublished - 2013 Jun

Bibliographical note

Funding Information:
This work was supported by National Research Foundation of Korea Grant funded by the Korean Government (MEST) ( 2010-0019923 ), the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) ( 2012050077 ). This study was also supported by a grant from the National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea ( 1020390 ). We are grateful to Yonsei-Carl Zeiss Advanced Imaging Center, Yonsei University College of Medicine, for technical assistance.

All Science Journal Classification (ASJC) codes

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

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