Nano-based strategies to overcome p-glycoprotein-mediated drug resistance

ABSTRACT

Introduction: The discussion about cancer treatment has a long history. Chemotherapy, one of the promising approaches in cancer therapy, is limited in the clinic as plenty of factors evolve and prevent appropriate therapeutic response to drugs. Multi-drug resistance (MDR), which is mostly P-glycoprotein-mediated, is described as the most well-known impediment in this contribution. It extrudes several agents out of cells, arising MDR and decreasing the bioavailability of drugs. Hence, cancer cells become insensitive to chemotherapy.

Areas covered: Many agents have been developed to reverse MDR, but it is difficult to deliver them into cancer sites and cancer cells. The emerging nano-based drug delivery systems have been more effective to overcome P-glycoprotein-mediated MDR by increasing the intracellular delivery of these agents. Here, we represent systems including siRNA-targeted inhibition of P-gp, monoclonal antibodies, natural extracts, conventional inhibitors, hard nanoparticles and soft nanoparticles as delivery systems in addition to a novel approach applying cell penetrating peptides.

Expert opinion: Overcoming cancer drug resistance using innovative nanotechnology is being increasingly used and developed. Among resistance mechanisms, drug efflux transporter inhibitors and MDR gene expression silencing are among the those being investigated. In the near future, it seems some of these nanomedical approaches might become the mainstay of effective treatment of important human conditions like cancer.

KEYWORDS:

• Cancer
• chemotherapy
• multi drug resistance
• nanomedical approaches
• P-glycoprotein

Article highlights

• Multidrug resistance of cancer cells is still an impediment for successful chemotherapy.

• Among various mechanisms responsible for multidrug resistance, membrane efflux pumps. Specially P-gp, have been widely investigated.

• To improve therapeutic efficacy of cancer drugs and reduce their cytotoxicity to normal cells, nano systems have been introduced as effective strategy.

• Modified cell penetrating peptides are the most novel cargos for intracellular delivery of cancer agents with different molecular weights.

• Investigating cellular uptake of nanoparticles can aid in bringing them faster into clinical use.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.