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Co-delivery of paclitaxel and survivin shRNA by pluronic P85-PEI/TPGS complex nanoparticles to overcome drug resistance in lung cancer

Paper ID Volume ID Publish Year Pages File Format Full-Text
6926 524 2012 12 PDF Available
Title
Co-delivery of paclitaxel and survivin shRNA by pluronic P85-PEI/TPGS complex nanoparticles to overcome drug resistance in lung cancer
Abstract

Drug resistance is a main obstacle for the successful chemotherapy of lung cancer. In this work, a new co-delivery system, P85-PEI/TPGS/PTX/shSur complex nanoparticles (PTPNs), to overcome paclitaxel (PTX) resistance in A549 human lung cancer was designed and developed. The experimental results showed that PTPNs could facilitate drug into cells and induce survivin shRNA (shSur) into nuclei on A549 and A549/T cells, achieve efficient gene delivery and induce availably RNA interference on A549/T cells. The IC50 of PTPNs against A549/T cells was 360-fold lower than that of free PTX. The enhanced efficacy of PTPNs against A549/T cells was associated with PTX-induced apoptosis and cell arrest in G2/M phase. Down-regulation of survivin protein by PTPNs could lower the apoptosis threshold of drug resistant cells and render chemotherapeutic agents more effective. Moreover, the inhibition of GST activity by P85 was found to increase PTX accumulation in A549/T cells. The in vivo antitumor efficacy showed that PTPNs were more effective than that of the Taxol. As a result, the co-delivery of PTX and shSur by PTPNs could be a very powerful approach to improve the therapeutic effect of PTX in resistant lung cancer.

Keywords
Drug resistance; Co-delivery; Paclitaxel; Survivin shRNA; Pluronic P85
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Co-delivery of paclitaxel and survivin shRNA by pluronic P85-PEI/TPGS complex nanoparticles to overcome drug resistance in lung cancer
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 33, November 2012, Pages 8613–8624
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