Nanotherapeutics in multidrug resistance

Abstract

The development of resistance to a variety of chemotherapeutic agents, also known as multidrug resistance (MDR), is a main impediment to the success of cancer chemotherapy, which refers to many factors such as increased efflux, blocked apoptosis, decreased drug influx, and altered cell cycle regulation. Considerable efforts have been devoted to develop chemosensitizers to conquer drug resistance, while their safety and unwanted pharmacokinetic drug interaction hindered their clinical applicability. Nano-sized drug carriers have great superiority in overcoming drug resistance due to the improved therapeutic index of drugs, enhanced drug targeting in tumor sites, and success in escaping from recognition of ABC transporter-mediated drug efflux. This chapter summarizes the most recent developments in the field of nanotherapeutics toward overcoming drug resistance by drug-targeted delivery, increased intracellular availability, changed subcellular localization, and combination of drug delivery with the agents that regulate intracellular pH, energy delivery, and apoptotic threshold.