Cancer Photothermal Therapy with ICG-Conjugated Gold Nanoclusters

The coming era of precision nanomedicine demands engineered nanoparticles that can be readily translated into the clinic, like that of molecular agents, without being hindered by intrinsic size heterogeneity and long-term body retention. Herein we report that conjugation of indocyanine green (ICG), an FDA-approved near-infrared (NIR) dye, onto an atomically precise glutathione-coated Au25 (GS-Au25) nanocluster led to a molecular-like photothermal nanoparticle (ICG₄-GS-Au25) with significantly enhanced ICG photostability and tumor targeting. Under weak NIR light irradiation conditions, free ICG failed to suppress tumor growth but the original tumors were completely eradicated with ICG₄-GS-Au25. In the meantime, "off-target" ICG₄-GS-Au25 was effectively cleared out from the body like small-molecule drugs after glutathione-mediated biotransformation in the liver. These findings highlight the merits of molecular-like nanomedicines, offering a new pathway to meet FDA's criteria for the clinical translation of nanomedicines.