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

Wang, Junling, Wang, Ran, Zhang, Fangrong, Yin, Yajun, Mei, Leixia, Song, Fengjuan, Tao, Mingtao, Yue, Wanqing, Zhong, Wenying
Journal of materials chemistry B 2016 v.4 no.36 pp. 6043-6051
P-glycoproteins, carbon, drug delivery systems, drug therapy, etoposide, irradiation, ligands, monoclonal antibodies, multiple drug resistance, near infrared radiation, neoplasms, oxidation, photothermotherapy, polyethylene glycol, synergism
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.