In vitro and in vivo study of theranostic silver sulfide nanoparticles loaded with methotrexate for synchronous chemoradiation.

Aims: The development of multifunctional nanoplatforms capable of simultaneous therapeutic and diagnostic applications is a growing focus in biomedical research.

Methods/materials: In this study, silver sulfide - silver nanoparticles coated with bovine serum albumin (Ag₂S-Ag@BSA) were synthesized via a one-step biomineralization method at room temperature. Methotrexate (MTX), a chemotherapeutic agent, was chemically conjugated to the nanoparticles to enhance targeted anticancer activity. Comprehensive characterization using FTIR, UV-Vis, XRD, TEM, and DLS confirmed successful synthesis.

Results: TEM analysis revealed spherical nanoparticles with an average diameter of 12.02 nm, while DLS indicated a hydrodynamic size of 40 nm, a polydispersity index of 0.20, and a zeta potential of -24 mV, reflecting good stability. Drug release studies demonstrated enzyme-responsive behavior, with significantly increased MTX release in the presence of proteinase K, simulating intracellular protease activity. In vitro and in vivo assessments revealed that the combined treatment strategy - including MTX delivery, X-ray exposure, and radiosensitization - achieved superior therapeutic outcomes compared to monotherapies. Histopathological analysis confirmed the biocompatibility of the nanoplatform, with no observable tissue damage. Furthermore, the nanoparticles exhibited potential as computed tomography (CT) contrast agents.

Conclusion: These results suggest that Ag₂S-Ag@BSA-MTX nanoparticles offer a promising multifunctional approach for cancer theranostics.