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Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment

Paper ID Volume ID Publish Year Pages File Format Full-Text
5549 397 2015 12 PDF Available
Title
Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment
Abstract

Multidrug resistance (MDR) remains the primary issue in cancer therapy, which is characterized by the overexpressed P-glycoprotein (P-gp)-included efflux pump or the upregulated anti-apoptotic proteins. In this study, a D-alpha-tocopheryl poly (ethylene glycol 1000) succinate (TPGS) and hyaluronic acid (HA) dual-functionalized cationic liposome containing a synthetic cationic lipid, 1,5-dioctadecyl-N-histidyl-l-glutamate (HG2C18) was developed for co-delivery of a small-molecule chemotherapeutic drug, paclitaxel (PTX) with a chemosensitizing agent, lonidamine (LND) to treat the MDR cancer. It was demonstrated that the HG2C18 lipid contributes to the endo-lysosomal escape of the liposome following internalization for efficient intracellular delivery. The TPGS component was confirmed able to elevate the intracellular accumulation of PTX by inhibiting the P-gp efflux, and to facilitate the mitochondrial-targeting of the liposome. The intracellularly released LND suppressed the intracellular ATP production by interfering with the mitochondrial function for enhanced P-gp inhibition, and additionally, sensitized the MDR breast cancer (MCF-7/MDR) cells to PTX for promoted induction of apoptosis through a synergistic effect. Functionalized with the outer HA shell, the liposome preferentially accumulated at the tumor site and showed a superior antitumor efficacy in the xenograft MCF-7/MDR tumor mice models. These findings suggest that this dual-functional liposome for co-delivery of a cytotoxic drug and an MDR modulator provides a promising strategy for reversal of MDR in cancer treatment.

Keywords
Liposome; Paclitaxel; Lonidamine; Combination therapy; Multidrug resistance
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Reversal of multidrug resistance by co-delivery of paclitaxel and lonidamine using a TPGS and hyaluronic acid dual-functionalized liposome for cancer treatment
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 73, December 2015, Pages 284–295
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