Abstract：
Compared 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.
摘要：
与常规疗法相比,光免疫疗法提供精确的靶向癌症治疗，对健康组织的损害最小，副作用减少，但其疗效可能受到浅层光穿透和潜在肿瘤耐药的限制。这里,一种受体-供体-受体（A-D-A）结构的纳米聚集体是通过双重光疗开发的，包括光动力疗法（PDT）和光热疗法（PTT），由单个近红外（NIR）光触发。受益于强大的分子内电荷转移（ICT），A-D-A结构的纳米聚集体表现出广泛的吸收延伸到NIR区域并有效抑制荧光，这使得深穿透和有效的光热转化(η=67.94%)。合适的HOMO-LUMO分布有助于充分的系统间交叉（ISC），以将基态氧（3O2）转化为单线态氧（1O2）和超氧化物阴离子（·O2-），并催化羟基自由基(·OH)的产生。增强的ICT和ISC效应赋予A-D-A结构化纳米聚集体有效的PTT和PDT治疗宫颈癌，诱导有效的免疫原性细胞死亡。结合临床铝佐剂凝胶，在原位和腹膜内转移宫颈癌动物模型中，开发了一种新的宫颈癌光免疫治疗策略，并证明该策略可显著抑制原发性和转移性肿瘤。无创治疗策略为临床早期和晚期宫颈癌治疗提供了新的见解。
