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Tailoring nanostructured solid-lipid carriers for time-controlled intracellular siRNA kinetics to sustain RNAi-mediated chemosensitization

Paper ID Volume ID Publish Year Pages File Format Full-Text
8112 577 2011 11 PDF Available
Title
Tailoring nanostructured solid-lipid carriers for time-controlled intracellular siRNA kinetics to sustain RNAi-mediated chemosensitization
Abstract

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.

Keywords
Small-interfering RNA; Drug delivery; Lipid nanoparticles; Cancer chemotherapy; Chemosensitization; SurvivinCA, cetyl alcohol; DC-liposomes, DOTAP/cholesterol liposomes; DOTAP, 1,2-dioleoyl-3-trimethylammonium-propane; LAL, lysosomal acid lipase; MTT, 3-(
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Tailoring nanostructured solid-lipid carriers for time-controlled intracellular siRNA kinetics to sustain RNAi-mediated chemosensitization
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 10, April 2011, Pages 2662–2672
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us