Synthesis and Optical Properties of Two-Photon-Absorbing Au₂₅(Captopril)₁₈-Embedded Polyacrylamide Nanoparticles for Cancer Therapy

Au25(Captopril)18 nanoclusters (NCs) are a 1.2 nm water-soluble metal nanomaterial with strong two-photon absorption, with excited-state reactive oxygen production, and of potential applicability for biomedical imaging and two-photon photodynamic therapy (2p-PDT). Because of the low cellular uptake of Au25(Captopril)18 clusters, its limited potential for conjugation with targeting agents, and to enhance its biocompatibility, we embedded these clusters into hydrogel nanoparticles (NPs) by synthesizing polyacrylamide-encapsulated Au25(Capt)18 nanoparticles (PAAm-Au25(Capt)18 NPs). We verified that the two-photon absorption and singlet oxygen production of these PAAm-Au25 NPs still exhibit the favorable properties of the original metal nanocluster. Furthermore, the Au25-encapsulated polyacrylamide nanoparticles have enhanced in vitro cell uptake, can be easily conjugated to targeting moieties, and exhibit significantly higher biocompatibility. Photoirradiation experiments on HeLa cancer cells incubated with these PAAm-Au25(Capt)18 NPs reveal excellent 2p-PDT efficacy, in contrast to 1p-PDT, thus demonstrating their promising potential for cancer PDT with infrared light that penetrates deeply into live tissue.