Molecular-Architectonics of Gold Nanoclusters for enhanced fluorescence and photosensitizing property for Image Guided Photodynamic Therapy of Hypoxic Tumor

Gold nanoclusters (AuNCs) comprising a metal core of few atoms and a shell of thiols have unique photoluminescence unlike its bigger counterparts. Due to the ligand-to-metal charge transfer, long-lived excited state and excited triplet state has been exhibited by some metal clusters attributing to their inherent photosensitizing (PS) property. Hence, AuNCs have significant impact in biomedical domains like image assisted photodynamic therapy (PDT). In this work, the molecular nanoarchitectonics of self assembled cysteine-capped AuNCs has been tailored to improve its photosensitizing and emission properties for PDT and simultaneous imaging applications. The unique molecular nanoarchitectonics contributed to the aggregation induced emission (AIE) property of gold cluster contributing to the enhanced photosensitizing and bio-imaging property. We performed in-silico model to study the interaction of cysteine to gold cluster, its ground and excited-state properties, and the charge transfer mechanism. Cysteine-capped AuNCs yielded efficient generation of cytotoxic radicals which has contributions from the dispersed independent gold cluster as well as the self assembled nanoarchitecture. Thus, the cysteine-capped AuNCs could generate free radicals for cancer therapy by both Type I and Type II photosensitizing pathways, with the Type I reaction relevant for use in the hypoxic tumour environment. The metal cluster also exhibited excellent biocompatibility in cancer cells. The image-guided photodynamic exhibited significant cell death after 60s laser irradiation. Thus, the unique molecular nanoarchitectonics of the synthesised AuNCs has resulted in a promising new theranostic nano-platform with potential clinical applications.