Nanomedicinal Strategies to Treat Multidrug-Resistant Tumors: Current Progress

Abstract

Multidrug resistance (MDR) is a major impediment to the success of cancer chemotherapy. Pglycoprotein is an important and the best-known membrane transporter involved in MDR. Several strategies have been used to address MDR, especially P-glycoprotein-mediated drug resistance in tumors. However, clinical success has been limited, largely due to issues regarding lack of efficacy and/or safety. Nanoparticles have shown the ability to target tumors based on their unique physical and biological properties. To date, nanoparticles have been investigated primarily to address P-glycoprotein and the observed improved anticancer efficacy suggests that nanomedicinal strategies provide a new opportunity to overcome MDR. This article focuses on nanotechnology-based formulations and current nanomedicine approaches to address MDR in tumors and discusses the proposed mechanisms of action.

Special AT-rich sequence binding protein 1 regulates the multidrug resistance and invasion of human gastric cancer cells

“…A similar finding has been reported in breast cancer cells (25). ABC transporters usually function as pumps that remove toxins and drugs from the cells and p-glycoprotein (p-gp) and MDR-1 are the most characterized ABC transporters (26). Studies should therefore be conducted to investigate the effect of SATB1 on the expression of p-gp and MDR-1, in order to elucidate whether SATB1 contributes to MDR by modulating the expression of ABC transporters and the intracellular accumulation of drugs.…”

Inclusion of a pH-responsive amino acid-based amphiphile in methotrexate-loaded chitosan nanoparticles as a delivery strategy in cancer therapy

“…Here, the enhanced cytotoxicity of MTX via the pH-responsive NPs means that a significant reverse effect of drug resistance could has occurred. Moreover, nanoparticulated systems may reduce the resistance effects that characterize many anticancer drugs by a mechanism of cell internalization of the drug by endocytosis, by lowering drug efflux from the cells and, in the case of pH-responsive NPs, by allowing an effective drug release from the endosomes to cell cytosol (Dong and Mumper 2010). Therefore, the pHdependent membrane-lytic activity of the MTX-CS-NPs (see the previous section) seems to be directly related with their enhanced therapeutic efficacy compared to the native drug.…”

“…The clinical efficacy of the conventional treatments is often compromised by the acquisition of resistance in cancer cells and/or by the generation of several side effects to the patients (Banerjee et al 2002;Dong and Mumper 2010). In this context, the nanotechnology-based pharmaceutical products might provide a wide range of new tools and possibilities in cancer therapy, from earlier diagnostics to more efficient and more targeted treatments (Chen et al 2014;Das and Sahoo 2011;Li et al 2012).…”

Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

“…This poor prognosis is mainly due to MDR in gastric cancer cells. Many strategies have been developed to overcome MDR in cancer, including modification of chemotherapy regimens (Dong and Mumper, 2010), inactivation o MDR-associated genes (Kruhn et al, 2009;Stege et al, 2010), use of monoclonal antibodies for MDR1 (Goda et al, 2007), new inhibitors of ABC transporters (Dong and Mumper, 2010) and so on. However, there are numerous challenges for these strategies.…”