In this study, we successfully synthesized a small-sized gold nanocluster (2 nm) coated with homogeneous tripeptides bearing azido and amino groups that enable facile multifunctionalizations. Using sodium phenoxide to reduce tetrachloroauric(iii) acid in the presence of the cysteine-containing tripeptide, we efficiently prepared the gold nanoclusters without damaging the azido group. We then utilized this clickable bisreactive nanocluster as a versatile platform for synthesizing multifunctionalized gold nanomaterials. The resulting nanoclusters were conjugated with an anticancer compound connected to an indolizine moiety for photoinduced uncaging, a photodynamic therapy agent acting as a photosensitizer for uncaging, and a cyclic RGD peptide. The cytotoxicity of the multifunctionalized gold nanoclusters was demonstrated through red light irradiation of human lung cancer-derived A549 cells treated with the synthesized nanomaterials. The significant cytotoxicity exhibited by the cells underscores the potential utility of this method in advanced cancer therapies.
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