Water-dispersible CuS nanoparticles are developed by the soft chemical approach using phosphorylethanolamine as a surface passivation agent for chemo–photothermal therapy and photoacoustic application.

Photothermal therapy (PTT) is a promising treatment option for cancer. However, biocompatibility, water dispersibility, and good photoresponsiveness are necessary for photothermal agents to be used in PTT. Herein, a soft chemical approach is reported for the design and development of phosphorylethanolamine-functionalized CuS nanoparticles (PEA-CuS NPs) using phosphorylethanolamine (PEA) as a surface passivation agent for combinatorial chemo–photothermal therapy. X-ray diffraction and transmission electron microscopy analyses proved the successful formation of the green covellite CuS phase with an average particle size of 13 nm, while Fourier transform infrared spectroscopy and light scattering measurements demonstrated their surface functionalization with the PEA ligand. The PEA-CuS NPs have exhibited good photothermal heating efficacy upon irradiation of 980 nm laser light. Moreover, the in vitro studies have shown substantial cellular uptake of PEA-CuS NPs in MCF-7 cell lines and their dose-dependent cytotoxicity (83.3 and 65.4% cell-killing efficacy by 100 and 50 μg mL⁻¹ of PEA-CuS NPs, respectively) upon 980 nm laser irradiation (0.65 W power). The developed PEA-CuS NPs have also demonstrated very high acoustic signal under 690 and 530 nm laser light irradiation. Thus, these water-dispersible PEA-CuS NPs can be served as a promising candidate for image-guided combinatorial therapy involving chemotherapy and PTT.