An assessment of functionalised gold nanoclusters for the delivery of doxorubicin to a breast cancer cell model.

Abstract

Nanotechnology, a rapidly growing field of science, encompasses manipulating materials at the nanoscale with varied applicability to everyday situations. The advent of nanotechnology has facilitated the formulation of novel delivery systems for bioactive molecules. Gold nanoclusters have lured researchers in the field of nanomedicine due to their attractive qualities, which include ultra-small size, photostability, biocompatibility, and efficiency in drug delivery to tumour sites. Breast cancer is among the most common cancers affecting women globally and is a leading cause of death. Chemotherapeutic agents have been traditionally used to treat breast cancer. The anticancer drugs’ low solubility is due to their hydrophobic nature, and their non-targeted delivery results in toxicity and high levels of drug resistance. Hence, the need for a smart and efficient drug delivery system is necessary to reduce toxicities and improve therapeutic efficiency. Gold nanoclusters (AuNCs) were synthesised successfully using glutathione, followed by encapsulation using the polymer, chitosan (CS), which was conjugated to the anticancer drug doxorubicin (DOX). High encapsulation was observed, with 83 % for the Au-CS-DOX-loaded nanocomplex (AuCTD) compared to 68 % for the CS-DOX-loaded nanocomplex (CTD). Physicochemical characterisation included UV-visible spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and nanoparticle tracking analysis (NTA). All nanoparticles (NPs) and nanocomplexes were spherical, displayed hydrodynamic sizes of less than 150 nm, had good stability and were mostly monodisperse. Pharmacokinetic studies conducted at physiological and acidic pH levels revealed that the AuCTD nanocomplex displayed a more controlled drug release over time than the CTD nanocomplex. Cytotoxicity studies were conducted using the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay on the human embryonic kidney (HEK293) and breast adenocarcinoma (MCF-7) cells. The AuCTD nanocomplex showed greater anticancer activity (11.12 % cell survival) compared to the CTD nanocomplex (54.63 % cell survival) and free DOX (32.83 % cell survival) in the MCF-7 cells at the highest concentration of 40 μg/ml. The AuCTD complex showed little cytotoxicity in the HEK293 cells. The high apoptotic indices of the nanocomplex in the MCF-7 cells suggested that apoptosis was a possible mechanism of cell death. Both nanocomplexes displayed no significant differences in the cell cycle analysis, as treatment with both nanocomplexes induced the cells toremain in the G0/G1 cell cycle phase. Overall, the positive qualities of the AuCTD nanocomplex as a delivery system in vitro have been highlighted. These results warrant further studies to determine the mechanisms of action of the nanocomplex and to test these nanocomplexes in vivo using a breast cancer animal model.