Enhanced Systemic Anti-Angiogenic siVEGF Delivery Using PEGylated Oligo-D-arginine
- Authors
- Chung, Jee Young; Ul Ain, Qurrat; Lee, Hyun Lin; Kim, So-Mi; Kim, Yong-Hee
- Issue Date
- Sep-2017
- Publisher
- AMER CHEMICAL SOC
- Keywords
- angiogenesis; enhanced permeability and enhanced effect; siVEGF delivery; PEGylation; antitumor therapy
- Citation
- MOLECULAR PHARMACEUTICS, v.14, no.9, pp.3059 - 3068
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR PHARMACEUTICS
- Volume
- 14
- Number
- 9
- Start Page
- 3059
- End Page
- 3068
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/5382
- DOI
- 10.1021/acs.molpharmaceut.7b00282
- ISSN
- 1543-8384
- Abstract
- Angiogenesis mainly mediated by upregulation of vascular endothelial growth factor (VEGF) provides a hallmark of rapidly proliferating tumor cells and an essential component of the tumor growth and microenvironment, making it a targetable process for antitumor therapy. RNA interference (RNAi) provides a very effective tool for developing antitumor therapies; however, its application to date has been hampered due to the lack of efficient small interfering RNA (siRNA) delivery systems in vivo. Here, we report a polymeric gene carrier system based on PEGylation of a cationic cysteine-ended 9-mer arginine oligopeptide (CR9C), which provides effective siRNA systemic delivery and specifically suppresses VEGF (siVEGF). The PEG500-CR9C/siVEGF oligopeptoplex provided improved blood circulation, enhanced protection from serum proteases, reduced uptake in the liver and kidneys, enhanced tumor targeting, and down-regulated intratumoral VEGF level, which comprehensively resulted in improved antitumor efficacy without significant toxicity in vivo. PEG500-CR9C has a great potential for safe and efficient siRNA delivery with diverse applications.
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