Xiaoyuan Ji

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

AbstractPhotoagents 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.

An Acceptor–Donor–Acceptor Structured Nano‐Aggregate for NIR‐Triggered Interventional Photoimmunotherapy of Cervical Cancer

AbstractCompared with conventional therapies, photoimmunotherapy offers precise targeted cancer treatment with minimal damage to healthy tissues and reduced side effects, but its efficacy may be limited by shallow light penetration and the potential for tumor resistance. Here, an acceptor–donor‐acceptor (A‐D‐A)‐structured nanoaggregate is developed with dual phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), triggered by single near‐infrared (NIR) light. Benefiting from strong intramolecular charge transfer (ICT), the A–D–A‐structured nanoaggregates exhibit broad absorption extending to the NIR region and effectively suppressed fluorescence, which enables deep penetration and efficient photothermal conversion (η = 67.94%). A suitable HOMO–LUMO distribution facilitates sufficient intersystem crossing (ISC) to convert ground‐state oxygen (3O2) to singlet oxygen (1O2) and superoxide anions (·O2−), and catalyze hydroxyl radical (·OH) generation. The enhanced ICT and ISC effects endow the A–D–A structured nanoaggregates with efficient PTT and PDT for cervical cancer, inducing efficient immunogenic cell death. In combination with clinical aluminum adjuvant gel, a novel photoimmunotherapy strategy for cervical cancer is developed and demonstrated to significantly inhibit primary and metastatic tumors in orthotopic and intraperitoneal metastasis cervical cancer animal models. The noninvasive therapy strategy offers new insights for clinical early‐stage and advanced cervical cancer treatment.