Multifunctional hybrid nanoparticles based on sodium carboxymethylcellulose-graft-histidine and TPGS for enhanced effect of docetaxel

Abstract

Multifunctional hybrid nanoparticles (NPs) based on sodium carboxymethylcellulose-graft-histidine (CMH) and TPGS were designed for effective delivery and overcoming multidrug resistance (MDR) of docetaxel (DTX). An amphiphilic CMH copolymer with excellent biocompatibility, pH-sensitivity, and solubilizing capacity for poorly soluble drugs was firstly synthesized and characterized. TPGS incorporated into CMH copolymer facilitated lower critical aggregation concentration (CAC) (0.0074 mg mL⁻¹), smaller particle size (147.8 ± 3.14 nm), higher drug encapsulation (88.3 ± 3.33%), and better controlled release rate. The NPs based on CMH copolymer showed a pH-dependent drug release manner. The DTX-loaded CHT-1.5 NPs could significantly enhance cytotoxicity against both MCF-7 and MCF-7/ADR cells when compared to DTX-loaded CMH NPs and free DTX. Furthermore, cellular uptake and P-gp inhibition assays confirmed that the enhanced MDR reversal effect of DTX-loaded CHT-1.5 NPs was caused by the combination of increased drug accumulation and inhibition of P-glycoprotein mediated drug efflux in drug-resistant MCF-7/ADR cells. Consequently, CHT-1.5 NPs can act as an effective nanocarrier for delivering antitumor drugs and overcoming P-gp overexpressing tumor cells.