About the Influence of PEG Spacers on the Cytotoxicity of Titanate Nanotubes-Docetaxel Nanohybrids against a Prostate Cancer Cell Line.

Abstract

The association between chemotherapeutic drugs and metal oxide nanoparticles has sparked a rapidly growing interest in cancer nanomedicine. The elaboration of new engineered docetaxel (DTX)-nanocarriers based on titanate nanotubes (TiONts) was reported. The idea was to maintain the drug inside cancer cells and avoid multidrug resistance mechanisms, which often limit drug efficacy by decreasing their intracellular concentrations in tumor cells. HS-PEGn-COOH (PEG: polyethylene glycol, n = 3000, 5000, 10,000) was conjugated, in an organic medium by covalent linkages, on TiONts surface. This study aimed to investigate the influence of different PEG derivatives chain lengths on the TiONts colloidal stability, on the PEGn density and conformation, as well as on the DTX biological activity in a prostate cancer model (human PC-3 prostate adenocarcinoma cells). In vitro tests highlighted significant cytotoxicities of the drug after loading DTX on PEGn-modified TiONts (TiONts-PEGn-DTX). Higher grafting densities for shorter PEGylated chains were most favorable on DTX cytotoxicity by promoting both colloidal stability in biological media and cells internalization. This promising strategy involves a better understanding of nanohybrid engineering, particularly on the PEGylated chain length influence, and can thus become a potent tool in nanomedicine to fight against cancer.