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Modulation of Intracellular Ceramide using Polymeric Nanoparticles to Overcome Multidrug Resistance in Tumor Cells

L.E. van Vlerken, D. Shenoy, Z. Duan, M. Seiden, S. Mehta and M.M. Amiji
Northeastern University, US

Keywords:
MDR, apoptosis, nanoparticles, ovarian cancer

Abstract:
This work describes the formulation of a nanoparticle drug delivery system to co-administer a chemotherapeutic, paclitaxel, and an MDR modulator, C6-ceramide, aimed at overcoming multidrug resistance (MDR) of solid tumors. MDR can arise through several molecular mechanisms, and often results from a combination of these cellular alterations. The nanoparticle formulation described in this work aimes to suppress MDR by delivering the drugs intracellularly, thus bypassing ABC-transporter drug efflux, and by delivering exogenous ceramide to mend alterations in apoptotic signaling that occur in MDR cancer cells. In this study, the nanoparticle formulation was used to successfully revert chemoresistance in an MDR ovarian cancer cell line.

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