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自组装RNAi-金纳米颗粒纳米结构的抗肿瘤治疗应用：VEGF-RNAi与光热消融的联合应用

Antitumor therapeutic application of self-assembled RNAi-AuNP nanoconstructs: Combination of VEGF-RNAi and photothermal ablation.

作者信息

Son Sejin, Kim Namho, You Dong Gil, Yoon Hong Yeol, Yhee Ji Young, Kim Kwangmeyung, Kwon Ick Chan, Kim Sun Hwa

机构信息

These authors contributed equally.

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 6, Seongbuk-gu, Seoul 136-791, Republic of Korea.

出版信息

Theranostics. 2017 Jan 1;7(1):9-22. doi: 10.7150/thno.16042. eCollection 2017.

DOI:10.7150/thno.16042
PMID:28042312
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5196881/
Abstract

Nucleic acid-directed self-assembly provides an attractive method to fabricate prerequisite nanoscale structures for a wide range of technological applications due to the remarkable programmability of DNA/RNA molecules. In this study, exquisite RNAi-AuNP nanoconstructs with various geometries were developed by utilizing anti-VEGF siRNA molecules as RNAi-based therapeutics in addition to their role as building blocks for programmed self-assembly. In particular, the anti-VEGF siRNA-functionalized AuNP nanoconstructs can take additional advantage of gold-nanoclusters for photothermal cancer therapeutic agent. A noticeable technical aspect of self-assembled RNAi-AuNP nanoconstructs in this study is the precise conjugation and separation of designated numbers of therapeutic siRNA onto AuNP to develop highly sophisticated RNA-based building blocks capable of creating various geometries of RNAi-AuNP nano-assemblies. The therapeutic potential of RNAi-AuNP nanoconstructs was validated as well as by combining heat generation capability of AuNP and anti-angiogenesis mechanism of siRNA. This strategy of combining anti-VEGF mechanism for depleting angiogenesis process at initial tumor progression and complete ablation of residual tumors with photothermal activity of AuNP at later tumor stage showed effective tumor growth inhibition and tumor ablation with PC-3 tumor bearing mice.

摘要

由于DNA/RNA分子具有显著的可编程性，核酸定向自组装为制造适用于广泛技术应用的必要纳米级结构提供了一种有吸引力的方法。在本研究中，除了作为程序性自组装的构建块外，还利用抗VEGF siRNA分子作为基于RNAi的治疗剂，开发了具有各种几何形状的精致RNAi-AuNP纳米结构。特别地，抗VEGF siRNA功能化的AuNP纳米结构可以利用金纳米团簇作为光热癌症治疗剂的额外优势。本研究中自组装RNAi-AuNP纳米结构的一个显著技术方面是将指定数量的治疗性siRNA精确缀合到AuNP上并从其上分离，以开发能够创建各种几何形状的RNAi-AuNP纳米组装体的高度复杂的基于RNA的构建块。RNAi-AuNP纳米结构的治疗潜力通过结合AuNP的发热能力和siRNA的抗血管生成机制得到了验证。这种在肿瘤进展初期结合抗VEGF机制以耗尽血管生成过程，并在肿瘤后期利用AuNP的光热活性完全消融残余肿瘤的策略，在携带PC-3肿瘤的小鼠中显示出有效的肿瘤生长抑制和肿瘤消融效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c60b/5196881/ea5a9be09bfb/thnov07p0009g008.jpg
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