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Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers

Paper ID Volume ID Publish Year Pages File Format Full-Text
6469 491 2013 13 PDF Available
Title
Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers
Abstract

Pluronics have been demonstrated as excellent multidrug resistance (MDR) reversal agent in the form of unimers rather than micelles. However, the effective intracellular delivery of Pluronic® unimers to MDR cancer cells still remains a big challenge. To address this issue, a mixed micellar system based mainly on the pH-sensitive copolymer of poly (l-histidine)-poly (d,l-lactide)-polyethyleneglycol-poly (d,l-lactide)-poly (l-histidine) (PHis-PLA-PEG-PLA-PHis) and Pluronic® F127, some of which was conjugated with folate, was constructed to intracellularly deliver the unimers of Pluronic® P85 to MDR cells. The folate-mediated endosomal pH-sensitive mixed micelles (pHendoSM-P85/f) were prepared by a thin-film hydration method, by which Pluronic® P85 unimers and doxorubicin (DOX) were incoporated into the mixed micelles. The incorporation of Pluronic® P85 unimers was investigated by the surface tension test. The results indicated that the Pluronic® P85 unimers probably first inserted into the binary mixed micelles and then formed a triple-component mixed micelles with Pluronic® F127 and PHis-PLA-PEG-PLA-PHis as the loading content increased. Further analyzed with flow cytometry, confocal laser scanning microscopy (CLSM) and MTT assay, the micelles with inserted Pluronic® P85 unimers demonstrated much more cellular uptake and higher cytotoxicity against MDR cells than the triple-component mixed micelles and plain Pluronic® micelles. The enhanced MDR reversal effect was attributed to the successful intracellular delivery of Pluronic® P85 unimers to the MDR cells, which was confirmed by the subcellular colocalization of Pluronic® P85 unimers with mitochondria, the decreased ATP energy and mitochondrial membrane potential (MP) in the MCF-7/ADR cells. The pHendoSM-P85/f/DOX also demonstrated more dramatic antitumor efficiency and remarkable reduction of ATP energy in the MDR cells in tumors than the control formulations. The intracellular delivery of Pluronic® P85 unimers to the MDR cells based on the targeted and endosomal pH triggerd release mixed micelles has been demonstrated as a promising approach to reverse MDR.

Keywords
Pluronic® P85 unimers; Multidrug resistance; Intracellular delivery; Triggered release; pH sensitive
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Reversing multidrug resistance by intracellular delivery of Pluronic® P85 unimers
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 34, Issue 37, December 2013, Pages 9602–9614
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