Synthesis and Characterization of Thiol-Protected Silver Nanoclusters for Photodynamic Therapy Applications

Abstract

Aqueous metal nanoclusters have emerged as versatile tools in biomedical applications, particularly in the scope of imaging and cancer therapeutics. This research paper investigates a thiol-protected silver nanocluster (AgNC), focusing on establishing a reproducible synthesis method to obtain a pure cluster species for use in biological stability studies. Conventionally, nanocluster synthesis employs reducing agents, like NaBH4, which often poses challenges in reaction control and product purity. This study adopts an alternative approach, utilizing a Norrish Type I reaction to enhance synthesis. This light-activated reaction leverages the regulated concentration of alpha-hydroxy radicals from a photoinitiator (Omnirad 2959) achieved through UVA-induced homolytic bond cleavage. Monitoring AgNC formation through ultraviolet-visible (UV-Vis) and fluorescence emission-excitation matrix (EEM) spectroscopy and confirming product purity via parallel factor analysis (PARAFAC), this work offers insight into the influence of parameters such as light intensity, reactant concentration, irradiation wavelength, and oxygen presence on consistency and reproducibility of the AgNC syntheses. Methods like Polyacrylamide Gel Electrophoresis (PAGE) and centrifugation are also employed to facilitate separation and purification, preparing the AgNC for subsequent evaluation within biologically significant contexts (tumor microenvironments and phosphate buffer solutions). Although diverse reaction conditions yielded an array of nanocluster species, characterization of the AgNCs reveals challenges in reproducing a pure cluster species consistently. EEM and PARAFAC analyses underscore similarities across synthesized clusters, yet significant variations in reaction conditions persist. The primary application envisioned for these AgNCs is in Photodynamic Therapy (PDT), a form of radiative therapy that exploits the optical properties of metal nanoclusters to induce reactive oxygen species, thus eliciting cancer cell death. It is evident that further investigation is necessary to deepen the comprehension of AgNCs and validate their potential use in PDT. Future research should focus on refining reaction conditions, and effective separation, of AgNC, allowing for advancement in therapeutic interventions such as PDT.