Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles

Title
Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles
Authors
김선화김명구조성덕이지영이범석이소진박성걸강선웅정지훈
Keywords
VEGF; Anti-angiogenesis; Bevacizumab; siRNA; Drug delivery
Issue Date
2017-07
Publisher
Biochemical and biophysical research communications
Citation
VOL 489, NO 1-41
Abstract
A variety of VEGF inhibitors have been reported to treat cancers by suppressing tumor angiogenesis. Bevacizumab, a monoclonal VEGF antibody, was the first FDA approved anti-angiogenic agent for cancer treatments. However, bevacizumab shows modest therapeutic efficiency and often cause resistant problem in significant populations of cancer patients. To solve these problem, we investigated the therapeutic efficacy of siRNA drugs targeting VEGF and combination of the RNAi drug with bevacizumab for cancer treatments. For efficient VEGF siRNA delivery, chemically polymerized siRNAs were complexed with thiolated-glycol chitosan (psi(VEGF)/tGC). The poly-VEGF siRNA and thiolated-glycol chitosan formed stable nanoparticles via electrostatic interaction and chemical crosslinking, and showed high accumulation in tumor tissues resulting in efficient gene silencing. Both VEGF siRNA nanoparticles and bevacizumab had efficient therapeutic effects in tumor xenograft mouse models. Interestingly, most pronounced therapeutic efficacy was observed when the two distinct VEGF inhibitors were treated in combination revealing synergistic effects. The results showed that the psi(VEGF)/tGC nanoparticle mediated knockdown of VEGF exerts anti-tumor effects and the combination treatments with bevacizumab can extend the treatments options to conventional bevacizumab treatments for cancer therapy.
URI
http://pubs.kist.re.kr/handle/201004/66689
ISSN
0006-291X
Appears in Collections:
KIST Publication > Article
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