Overcoming multidrug resistance by a combination of chemotherapy and photothermal therapy mediated by carbon nanohorns

Abstract

Multidrug resistance (MDR) is a major obstacle to cancer chemotherapy due to the overexpression of P-glycoprotein (P-gp). Herein, etoposide (ETO) was loaded onto oxidized carbon nanohorns (oxCNHs), which were modified by polyethylene glycol (PEG) and further functionalized with the targeting ligand P-gp monoclonal antibody (PA) in an attempt to overcome MDR. The obtained drug delivery system (ETO@oxCNHs/PEG-PA) showed high drug loading efficiency, enhanced drug release under laser irradiation, improved cellular uptake and increased therapeutic effect both in vitro and in vivo. In addition, NIR laser irradiation had a synergistic effect on overcoming MDR. The MDR-overcoming mechanism could be the efficient cellular uptake, enhanced drug release and reduced drug efflux by P-gp. These results demonstrated that ETO@oxCNHs/PEG-PA could be a promising drug delivery system for cancer MDR reversion.