Overcoming multidrug resistance (MDR) in breast cancers
Multidrug resistance (MDR) constitutes one of the major limitations for successful cancer treatment. MDR may occur because transporter proteins (e.g. P-glycoprotein), that expel drugs from cells are overexpressed on the surface of cancer cells. Expelling drugs inevitably lowers the therapeutic effect and cancer cells soon develop resistance to a variety of drugs.
This project is focused on the development and understanding of nanoparticle delivery systems of chemotherapy, primarily directed towards breast cancer treatment. We have developed a simple and reliable nanoparticle carrier system for doxorubicin that induces more apoptosis and can overcome multi drug resistance in breast cancer cells compared to free drug alone. We now focus our attention on the uptake and MDR mechanisms by blocking specific uptake routes, quantifying by FACS, confocal and western blotting with an aim of understanding the physiochemical properties that gives rise to the favourable effects and efficacy we observe. By gaining this fundamental understanding of the parameters of importance we will develop knowledge of mechanisms of overcoming MDR via nanomedical approaches that we can utilize to engineer drug delivery systems for other drugs than doxorubicin, and potentially in the future allow for new nanomedical therapeutics that do not suffer from MDR effects.
- Xianghui Zeng, and Andreas M. Nyström, Endocytic uptake and intracellular trafficking of bis-MPA based hyperbranched copolymer micelles in breast cancer cells, Biomacromolecules, 2012, 13, 3814-3822.
- P. Lundberg, N. A. Lynd, Y. Zhang, X. Zeng, D. V. Krogstad, T. Paffen, M. Malkoch, A. M. Nyström and C. J. Hawker pH-triggered self-assembly of biocompatible histamine-functionalized triblock copolymers, Soft Matter 2013, 9, 82-89.
- Xianghui Zeng, Yuning Zhang, Zhihua Wu, Pontus Lundberg, Michael Malkoch, and Andreas M. Nyström Hyperbranched copolymer micelles as delivery vehicles of doxorubicin in breast cancer cells, Journal of Polymer Science Part A: Polymer Chemistry, 2012, 50,
- Andreas M. Nyström, Zhiqiang Xu,, Jinqi Xu, Sara Taylor, Thalia Nittis, Jeffrey Leonard, Sheila Stewart, and Karen L. Wooley, SCKs as nanoparticle carriers of doxorubicin: Investigation of core composition on the loading, release and cytotoxicity profil