Research
Overcoming multidrug resistance (MDR) in breast cancers
Andreas Nyström
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 for chemotherapy, primarily directed towards breast cancer. 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 as compared to the free drug. We now focus on understanding uptake and MDR mechanisms by blocking specific uptake routes. The response is quantified by FACS, confocal microscopy, and western blotting. By gaining a fundamental understanding of parameters of importance for MDR we will develop nanomedical approaches to engineer drug delivery systems for other drugs than doxorubicin. The aim is to allow for new nanomedical therapeutics that do not suffer from MDR effects.
References:
- Zeng X, Zhang Y, Wu Z, Lundberg P, Malkoch M, Nyström AM (2012) “Hyperbranched copolymers micelles as delivery vehicles of doxorubicin in breast cancer cells”. J Pol Sci. Part A: Polymer Chemistry. 50:280-288. [Epub 2011 Oct 6]. DOI: 10.1002/pola.25027
- Nyström AM, Xu Z, Xu J, Taylor S, Nittis T, Leonard J, Stewart S, Wooley KL. (2008) “SCKs as nanoparticle carriers of doxorubicin: Investigation of core composition on the loading, release and cytotoxicity profiles”. Chem Commun. 30:3579-3581. (Highlighted in Chem Biol, issue 9, 2008).