Cetuximab decorated redox sensitive D-alpha-tocopheryl- polyethyleneglycol-1000-succinate based nanoparticles for cabazitaxel delivery: Formulation, lung targeting and enhanced anti-cancer effects

Abstract

This research work aims to fabricate cetuximab (CTX) decorated cabazitaxel (CBZ) loaded redox-sensitive D-alpha-tocopheryl-polyethyleneglycol-1000-succinate (TPGS-SS) nanoparticles (NPs) for epidermal growth factor receptor (EGFR)-targeted lung tumor therapy.The NPs were prepared using a dialysis bag diffusion method to produce, non-redox sensitive non targeted (TPGS-CBZ-NPs), redox-sensitive nontargeted (TPGS-SS-CBZ-NPs), and targeted redox-sensitive NPs (CTX-TPGS-SS-CBZ-NPs). Developed NPs were characterized for particle sizes, polydispersity, surface charge, surface morphologies, and entrapment efficiency. Moreover, additional in vitro studies have been conducted, including in vitro drug release, cytotoxicity, and cellular uptake studies.The particle size and charge over the surface were found to be in the range of 145.6 to 308.06 nm and -15 to -23 mV respectively. The IC₅₀ values of CBZ clinical injection (Jevtana®), TPGS-CBZ-NPs, TPGS-SS-CBZ-NPs, and CTX-TPGS-SS-NPs were found to be 17.54 ± 3.58, 12.8 ± 2.45, 9.28 ± 1.13 and 4.013 ± 1.05 µg/ml, suggesting the 1.37, 1.89 and 4.37-folds respectively, enhancement of cytotoxicity as compared to CBZ clinical injection, demonstrating a significant augmentation in cytotoxicity. In addition, the in-vitro cellular uptake investigation showed that CTX-TPGS-SS-CMN6-NPs accumulated significantly compared to pure CMN6, TPGS-CMN6-NPs, and TPGS-SS-CMN6-NPs in the A549 cells. Furthermore, the targeting efficiency of developed NPs were analysed by ultrasound/photoacoustic and IVIS imaging.

Keywords: A549 cell lines; Benzo(a)pyrene; Cetuximab; Lung cancer; Redox-sensitive; Ultrasound and Photoacoustic Imaging.