Overcoming multidrug resistance with nanomedicines

Abstract

Introduction: Cancer remains the leading cause of death worldwide. Numerous therapeutic strategies that include smart biological treatments toward specific cellular pathways are being developed. Yet, inherent and acquired multidrug resistance (MDR) to chemotherapeutic drugs remains the major obstacle in effective cancer treatments.

Areas covered: Herein, we focused on an implementation of nanoscale drug delivery strategies (nanomedicines) to treat tumors that resist MDR. Specifically, we briefly discuss the MDR phenomenon and provide structural and functional characterization of key proteins that account for MDR. We next describe the strategies to target tumors using nanoparticles and provide a mechanistic overview of how changes in the influx:efflux ratio result in overcoming MDR.

Expert opinion: Various strategies have been applied in preclinical and clinical settings to overcome cancer MDR. Among them are the use of chemosensitizers that aim to sensitize the cancer cells to chemotherapeutic treatment and the use of nanomedicines as delivery vehicles that can increase the influx of drugs into cancer cells. These strategies can enhance the therapeutic response in resistant tumors by bypassing efflux pumps or by increasing the nominal amounts of therapeutic payloads into the cancer cells at a given time point.

Keywords:

• cancer multidrug resistance
• drug targeting
• multidrug resistance efflux pumps
• nanomedicine

Acknowledgments

The authors wish to thank Varda Wexler for her help with the graphics and illustrations and the Peer laboratory members for helpful discussions. A Ganoth and KC Merimi have equally contributed to this work.

Declaration of interest

D Peer declares financial interest in Quiet Therapeutics Ltd. This work was supported in part by the grants from the Lewis Family Trust, the Israeli Centre of Research Excellence (I-CORE), Gene Regulation in Complex Human Disease, Center No 41/11; Israel Science Foundation (Award 181/10); FTA: Nanomedicine for Personalized Theranostics, and by The Leona M. and Harry B. Helmsley Nanotechnology Research Fund awarded to D Peer. A Ganoth and KC Merimi have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

This box summarizes key points contained in the article.