Preclinical safety assessment of red emissive gold nanocluster conjugated crumpled MXene nanosheets: a dynamic duo for image-guided photothermal therapy

Abstract

Red emissive gold nanoclusters have potential as biological fluorescent probes, but lack sufficient light-to-heat conversion efficiency for photothermal therapy (PTT). MXene nanomaterials, on the other hand, have shown promise in PTT due to their strong near-infrared absorption abilities, but their instability caused by restacking of the sheets can decrease their available surface area. One approach to address this issue is to design sheets with wrinkles or folds. However, the crumpled or 3D MXene materials reported in the literature are actually aggregates of multiple nanosheets rather than a single sheet that is folded. In this study, a modified method for crumpling a single MXene sheet and further conjugating it with red emissive gold nanoclusters and folic acid was developed. A detailed in vitro toxicity study was performed in various cell lines and cellular uptake in cancer cells was studied using AFM to understand its interaction at the nano–bio interface. The material also demonstrated excellent utility as a bioimaging and PTT agent in vitro, with its high fluorescence allowing bioimaging at a lower concentration of 12 μg mL⁻¹ and a photothermal conversion efficiency of 43.51%. In vitro analyses of the cell death mechanisms induced by PTT were conducted through studies of apoptosis, cell proliferation, and ROS production. In vivo acute toxicity tests were conducted on male and female Wistar rats through oral and intravenous administration (20 mg kg⁻¹ dose), and toxicity was evaluated using various measures including body weight, hematology, serum biochemistry, and H&E staining. The findings from these studies suggest that the MXene gold nanoconjugate could be useful in a range of biomedical applications, with no observed toxicity following either oral or intravenous administration.