Tailoring the Surface of Ag2S Nanoparticles for Targeted, Light-Triggered Eradication of Cancer Cells

Nanostructure-mediated targeted photothermal therapy (PTT) emerged as a minimally invasive frontier in precision oncology, offering the ability to ablate malignancies. The tailoring of the surface of nanostructures serves as the ultimate bridge between material design and targeted PTT. In this aspect, the surface of Ag2S nanoparticles (Ag2S NPs) was engineered with hydrophilic, organic architectures to achieve superior colloidal stability and selective cellular uptake, ultimately enabling light-triggered eradication of cancer cells. The successful formation of the monoclinic Ag2S phase was confirmed by XRD and TEM analyses, and its surface modification with cysteine was evident from FTIR and light scattering measurements. The developed water-dispersible and biocompatible cysteine-functionalized Ag2S NPs (Cy-Ag2S NPs) showed sufficient absorbance in near-infrared (NIR) region and also exhibited good photothermal heating efficacy under 808 nm laser light. In order to achieve site-selective targeting toward cancer cells, folic acid (FA) was introduced onto the surface of Cy-Ag2S NPs via EDC-NHS coupling. In vitro studies showed negligible cytotoxicity of FA-conjugated Cy-Ag2S NPs (FA@Cy-Ag2S NPs) under dark conditions, whereas pronounced cancer cell ablation was observed under NIR irradiation. Moreover, the FA@Cy-Ag2S NPs showed targeted behavior toward folate receptor (FR)-positive KB cells over FR-negative A549 cells through apoptotic induction, suggesting their potential application in targeted PTT.