Quinoidal Semiconductor Nanoparticles for NIR‐II Photoacoustic Imaging and Photoimmunotherapy of Cancer

Photoagents with ultra-high near-infrared II (NIR-II) light energy conversion efficiency hold great promise in tumor phototherapy due to their ability to penetrate deeper tissues and minimize damage to surrounding healthy cells. However, the development of NIR-II photoagents remain challenging. In this study, an all-fused-ring quinoidal acceptor-donor-acceptor (A-D-A) molecule, SKCN, with a BTP core is synthesized, and nanoparticles named FA-SNPs are prepared. The unique quinoidal structure enhances π-electron delocalization and bond length uniformity, significantly reducing the bandgap of SKCN, resulting in strong NIR-II absorption, a high molar extinction coefficient, and a photothermal conversion efficiency of 75.14%. Enhanced molecular rigidity also facilitates efficient energy transfer to oxygen, boosting reactive oxygen species generation. By incorporating the immunomodulator R848, FA-SRNPs nanoparticles are further developed, effectively modulating the tumor immune microenvironment by reducing Tregs and M-MDSCs infiltration, promoting dendritic cell maturation, M1 macrophage polarization, and activating CD8+ T cells and NK cells. Comprehensive studies using orthotopic ovarian cancer models demonstrated strong tumor targeting, photoacoustic imaging capabilities, and significant tumor suppression and metastasis inhibition, and also showing excellent therapeutic efficacy in an orthotopic breast cancer model. This study provides strong evidence for the potential application of quinoidal A-D-A molecules in cancer photoimmunotherapy.