Structural engineering of mitochondria-targeted Au-Ag2S photosensitizers for enhanced photodynamic and photothermal therapy

Much effort has been devoted to designing diverse photosensitizers for efficient photodynamic therapy (PDT) and photothermal therapy (PTT) performance. However, the effect of PS morphology on the PDT and PTT performance needs to be further explored. In this work, a photosensitizer, Au-Ag2S nanoparticles functionalized with indocyanine green, caspase-3 recognition peptides, and mitochondria-targeting peptides (AICM NPs) with different morphologies, including core-shell, eccentric core-shell-I, eccentric core-shell-II, and Janus morphologies, were synthesized to enhance PDT and PTT performance. Among them, AICM Janus NPs with enhanced charge-transfer efficiency and photothermal conversion demonstrate superior PDT and PTT performance compared to those of other morphologies. In addition, AICM NPs exhibit satisfactory surface-enhanced Raman scattering performance for in situ SERS monitoring of caspase-3 during PDT and PTT processes. After PDT and PTT treatment with AICM Janus NPs, the damaged mitochondria released caspase-3. AICM Janus NPs achieved a superior apoptosis rate in tumor cells in vitro. Furthermore, AICM Janus NPs treat the tumors in vivo within only 10 days, which is half the time reported in other work. The AICM NPs demonstrated superior therapeutic safety both in vitro and in vivo. This study investigates the effects of morphology-property-performance of photosensitizers on the PDT and PTT performances, which opens a new pathway toward designing photosensitizers for efficient PDT and PTT.