Biodegradable nanoparticle-mediated K-ras down regulation for pancreatic cancer gene therapy

Chengbin Yang, Rui Hu, Tommy Anderson, Yucheng Wang, Guimiao Lin, Wing Cheung Law, Wei Jen Lin, Quoc Toan Nguyen, Hui Ting Toh, Ho Sup Yoon, Chih Kuang Chen, Ken Tye Yong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

19 Citations (Scopus)

Abstract

RNA interference (RNAi) targeting the K-ras oncogene mutation in pancreatic cancer mediated by small interfering RNA (siRNA) transfection is a very promising treatment. However, the rapid degradation and negative charge of naked siRNAs restrict their direct delivery into cells. In this contribution, we propose a safe and effective transmembrane transport nanocarrier formulation based on a newly developed biodegradable charged polyester-based vector (BCPV) for K-ras siRNA delivery into pancreatic cancer cells. Our results have shown that these biodegradable and biocompatible vectors are able to transfect siRNAs targeting mutant K-ras into MiaPaCa-2 cells with high transfection and knockdown efficiency. More importantly, the RNAi process initiated a cascade gene regulation of the downstream proteins of K-ras associated with cell proliferation, migration, invasion and apoptosis. We observed that after the mutant K-ras siRNA transfection, the growth, migration and invasion of the MiaPaCa-2 cells were significantly reduced; also, the apoptosis of the pancreatic cancer cells was promoted. Although in vivo testing data are limited, we propose that the BCPV based nanoparticle formulation could be a promising candidate as non-viral vectors for gene therapy in clinical settings. This journal is
Original languageEnglish
Pages (from-to)2163-2172
Number of pages10
JournalJournal of Materials Chemistry B
Volume3
Issue number10
DOIs
Publication statusPublished - 14 Mar 2015

ASJC Scopus subject areas

  • Chemistry(all)
  • Biomedical Engineering
  • Materials Science(all)

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