Kim, Myung Goo Jo, Sung Duk Yhee, Ji Young Lee, Beom Suk Lee, So Jin Park, Sung Gull Kang, Sun-Woong Kim, Sun Hwa Jeong, Ji Hoon 2024-01-20T01:02:32Z 2024-01-20T01:02:32Z 2021-09-05 2017-07-15 0006-291X https://pubs.kist.re.kr/handle/201004/122519 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. (C) 2017 Published by Elsevier Inc. English ACADEMIC PRESS INC ELSEVIER SCIENCE ENDOTHELIAL GROWTH-FACTOR INTRACRINE VEGF CELLULAR UPTAKE CANCER ANGIOGENESIS RESISTANCE STABILITY DELIVERY Synergistic anti-tumor effects of bevacizumab and tumor targeted polymerized VEGF siRNA nanoparticles Article 10.1016/j.bbrc.2017.05.103 1 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.489, no.1, pp.35 - 41 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 489 1 35 41 scie scopus 000403855600006 2-s2.0-85019588751 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article ENDOTHELIAL GROWTH-FACTOR INTRACRINE VEGF CELLULAR UPTAKE CANCER ANGIOGENESIS RESISTANCE STABILITY DELIVERY VEGF Anti-angiogenesis Bevacizumab siRNA Drug delivery