Development of a Pt(II) compound based on indocyanine green@human serum albumin nanoparticles: integrating phototherapy, chemotherapy and immunotherapy to overcome tumor cisplatin resistance

Cisplatin resistance is the main cause for the failure of cancer therapy. To solve the problem, we proposed to develop a novel human serum albumin (HSA) nanoplatform to integrate chemotherapy, photothermal therapy (PTT) and immunotherapy. To this end, we obtained a platinum compound (C5) with significant cytotoxicity in the cisplatin-resistant SKOV-3 cells (SKOV-3/DDP), and then innovatively constructed photosensitizer (indocyanine green (ICG))-encapsulated HSA-C5 complex nanoparticles (ICG@HSA-C5 NPs). The ICG@HSA-C5 NPs exhibited excellent photothermal performances in vitro and in vivo. Importantly, the in vivo results revealed that HSA enhanced the antitumor effect of C5 and that the combination of chemotherapy and PTT could significantly inhibit cisplatin-resistant tumor growth and improved the targeting abilities of C5 and ICG, and reduced their side effects. We also confirmed that ICG@HSA-C5 NPs killed the SKOV-3/DDP cells via gasdermin E (GSDME)-mediated pyroptosis and pyroptosis-induced immune responses, thereby synergistically leading to the death of the SKOV-3/DDP cells.