Nanotoxicological Evaluation of Surface Engineered WS2 Quantum Dots in Male and Female Wistar Rats for Targeted Nucleus Imaging and Photothermal Therapy

Abstract

Tungsten disulfide (WS₂) quantum dots (QDs) hold significant promise for biomedical applications due to their unique optical and physicochemical properties. To enhance their in vivo stability, these QDs are commonly functionalized with polyethylene glycol (PEG), therefore understanding its influence on biocompatibility is crucial. Here, we report a water-based synthesis of quasi-spherical PEGylated WS₂ QDs through a hydrothermal route. Comprehensive characterization was performed to elucidate the role of PEG in the formation, passivation, and performance of the QDs. In vitro cellular studies of PEG_WS₂ QDs revealed negligible cytotoxicity, minimal reactive oxygen species generation, and enhanced hemocompatibility compared to unmodified WS₂ QDs, reflecting synergistic effects of size, shape, and surface chemistry. Confocal microscopy confirmed nuclear internalization of the QDs. Furthermore, PEG_WS₂ QDs exhibited efficient photothermal conversion, supporting their potential in photothermal therapy. The mechanism of photothermal-induced cytotoxicity was investigated through cell cycle analysis post laser irradiation. A significant G0/G1 phase arrest, suggesting apoptosis-mediated cell death provides deeper mechanistic insights into the biological response. Gender-specific acute toxicity and biodistribution studies in male and female Wistar rats (intravenous, 20 mg/kg) indicated no significant adverse effects, although sex-specific differences in organ biodistribution were observed. Collectively, these findings establish PEG_WS₂ QDs as a stable, biocompatible, and multifunctional nanoplatform with strong potential for next generation theranostic applications.