期刊
BIOMATERIALS
卷 32, 期 10, 页码 2662-2672出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2010.12.029
关键词
Small-interfering RNA; Drug delivery; Lipid nanoparticles; Cancer chemotherapy; Chemosensitization; Survivin
资金
- Pennsylvania CURE Tobacco Settlement Formula
Use of siRNA for silencing major oncogenic/chemoresistance targets such as survivin has strong potential for cancer therapy. However, a key clinical limitation is their short action, preventing them from sustaining their therapeutic RNA-interference activity for optimal chemosensitization. This issue is tackled from the perspective of intracellular siRNA kinetics using a novel lipid-based nanostructured siRNA carrier (NSC), which incorporates variable amount of oil phase into the solid-lipid matrix to modify its siRNA release behaviors. We demonstrate that by manipulating the degradation responses of NSC device to lysosomal enzyme, tailoring of intracellular siRNA kinetics is achievable. A tailored NSC design delivering survivin-siRNA can extend the survivin knockdown period to 9 days, translating into steady, effective in vitro and in vivo chemosensitization of prostate cancer to docetaxel for over a week. All in all, this new NSC design provides a convenient mean to set up a clinically more appealing weekly or longer dosing cycle for siRNA therapy, which addresses a significant unmet need for prostate cancer treatment and is potentially useful for other chronic disease conditions as well. (C) 2010 Elsevier Ltd. All rights reserved.
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