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The co-delivery of paclitaxel and Herceptin using cationic micellar nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
9437 629 2009 9 PDF Available
Title
The co-delivery of paclitaxel and Herceptin using cationic micellar nanoparticles
Abstract

We have recently reported micellar nanoparticles self-assembled from a biodegradable and amphiphilic copolymer poly{(N-methyldietheneamine sebacate)-co-[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium bromide] sebacate}, P(MDS-co-CES), which were able to deliver small molecular drugs and biomacromolecules such as genes and functional proteins individually or simultaneously into various types of cells. In this study, these cationic micellar nanoparticles were employed as carriers to co-deliver paclitaxel and Herceptin for achieving targeted delivery of paclitaxel to human epidermal growth factor receptor-2 (HER2/neu)-overexpressing human breast cancer cells, and enhanced cytotoxicity through synergistic activities. Paclitaxel-loaded nanoparticles have an average size less than 120 nm and a zeta potential of about 60 mV. Herceptin was complexed onto the surface of the nanoparticles. The drug-loaded nanoparticle/Herceptin complexes remained stable under physiologically-simulating conditions with sizes at around 200 nm. The nanoparticles delivered Herceptin much more efficiently than BioPorter, a commercially available lipid-based protein carrier, and displayed a much higher anti-cancer effectiveness. Twice-repeated daily treatment with Herceptin showed significantly higher cytotoxicity especially in HER2-overexpressing breast cancer cells when compared to single treatment. Anti-cancer effects of this co-delivery system was investigated in human breast cancer cell lines with varying degrees of HER2 expression level, namely, MCF7, T47D and BT474. The co-delivery of Herceptin increased the cytotoxicity of paclitaxel and this enhancement showed a dependency on their HER2 expression levels. Targeting ability of this co-delivery system was demonstrated through confocal images, which showed significantly higher cellular uptake in HER2-overexpressing BT474 cells as compared to HER2-negative HEK293 cells. This co-delivery system may have important clinical implications against HER2-overexpressing breast cancers.

Keywords
Co-delivery; Herceptin; Paclitaxel; Cationic micellar nanoparticles; Amphiphilic copolymer
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The co-delivery of paclitaxel and Herceptin using cationic micellar nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 30, Issue 5, February 2009, Pages 919–927
Authors
, , , , ,
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