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.

中文翻译：

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用于癌症 NIR-II 光声成像和光免疫治疗的喹状半导体纳米粒子


具有超高近红外 II （NIR-II） 光能转换效率的光试剂在肿瘤光疗中前景广阔，因为它们能够穿透更深的组织并最大限度地减少对周围健康细胞的损害。然而，NIR-II 光敏剂的开发仍然具有挑战性。在本研究中，合成了具有 BTP 核心的全熔环喹状受体-供体-受体 （A-D-A） 分子 SKCN，并制备了名为 FA-SNPs 的纳米颗粒。独特的喹状结构增强了π电子离域和键长均匀性，显著降低了 SKCN 的带隙，从而产生了较强的 NIR-II 吸收、高摩尔消光系数和 75.14% 的光热转换效率。增强的分子刚度还有助于将能量有效地转移到氧气中，从而促进活性氧的产生。通过掺入免疫调节剂 R848，FA-SRNPs 纳米颗粒得到进一步开发，通过减少 Tregs 和 M-MDSCs 浸润、促进树突状细胞成熟、M1 巨噬细胞极化以及激活 CD8+ T 细胞和 NK 细胞来有效调节肿瘤免疫微环境。使用原位卵巢癌模型的综合研究表明，原位卵巢癌模型具有很强的肿瘤靶向性、光声成像能力以及显著的肿瘤抑制和转移抑制作用，并且在原位乳腺癌模型中也显示出优异的治疗效果。这项研究为喹啉 A-D-A 分子在癌症光免疫治疗中的潜在应用提供了有力的证据。