Nanotoxicological evaluation of surface engineered WS2 quantum dots in male and female Wistar rats for targeted nucleus imaging and photothermal therapy.

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 the influence of PEG on biocompatibility is crucial. Here, we report a water-based synthesis of quasi-spherical PEGylated WS2 QDs through a hydrothermal route (PEG_WS2 QDs). Comprehensive characterization was performed to elucidate the role of PEG in the formation, passivation, and performance of the QDs. In vitro cellular studies of the 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, the PEG_WS2 QDs exhibited efficient photothermal conversion, supporting their potential in photothermal therapy. The mechanism of photothermal-induced cytotoxicity in cancer cells was investigated through cell cycle analysis following laser irradiation. A significant G0/G1 phase arrest, suggesting apoptosis-mediated cell death, provides deeper mechanistic insights into the biological response. Acute toxicity - study in male and female Wistar rats (intravenous, 20 mg kg-1) indicated no significant adverse effects. However, 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.