Abstract：
Photoimmunotherapy represents an innovative approach to enhancing the efficiency of immunotherapy in cancer treatment. This approach involves the fusion of immunotherapy and phototherapy (encompassing techniques like photodynamic therapy (PDT) and photothermal therapy (PTT)). Boron-dipyrromethene (BODIPY) has the potential to trigger immunotherapy owing to its excellent PD and PT efficiency. However, the improvements in water solubility, bioavailability, PD/PT combined efficiency, and tumor tissue targeting of BODIPY require introduction of suitable carriers for potential practical application. Herein, a disulfide bond-based hollow mesoporous organosilica (HMON) with excellent biocompatibility and GSH-responsive degradation properties was used as a carrier to load a bithiophene Aza-BODIPY dye (B5), constructing a sample chemotherapy reagent-free B5@HMON nanoplatform achieving triple-synergistic photoimmunotherapy. HMON, involving disulfide bond, is utilized to improve water solubility, tumor tissue targeting, and PD efficiency by depleting GSH and enhancing host-guest interaction between B5 and HMO. The study reveals that HMON\'s large specific surface area and porous properties significantly enhance the light collection and oxygen adsorption capacity. The HMON\'s rich mesoporous structure and internal cavity achieved a loading rate of B5 at 11 %. It was found that the triple-synergistic nanoplatform triggered a stronger anti-tumor immune response, including tumor invasion, cytokine production, calreticulin translocation, and dendritic cell maturation, eliciting specific tumor-specific immunological responses in vivo and in vitro. The BALB/c mouse model with 4T1 tumors was used to assess tumor suppression efficiency in vivo, showing that almost all tumors in the B5@HMON group disappeared after 14 days. Such a simple chemotherapy reagent-free B5@HMON nanoplatform achieved triple-synergistic photoimmunotherapy.
摘要：
光免疫疗法代表了提高癌症治疗中免疫疗法效率的创新方法。这种方法涉及免疫疗法和光疗的融合（包括光动力疗法（PDT）和光热疗法（PTT）等技术）。硼-二吡咯亚甲基（BODIPY）由于其出色的PD和PT效率而具有引发免疫疗法的潜力。然而,水溶性的改善，生物利用度，PD/PT综合效率，BODIPY和肿瘤组织靶向需要引入合适的载体以进行潜在的实际应用。在这里，以生物相容性和GSH响应降解性能优异的二硫键基中空介孔有机二氧化硅(HMON)为载体负载联噻吩Aza-BODIPY染料(B5),构建无样品化疗试剂的B5@HMON纳米平台，实现三重协同光免疫疗法。亲爱的,涉及二硫键，用于提高水溶性，肿瘤组织靶向，通过耗尽GSH和增强B5和HMO之间的主客体相互作用来提高PD效率。研究表明，HMON的大比表面积和多孔特性显着增强了光的收集和氧吸附能力。HMON富介孔结构和内腔的B5负载率为11%。研究发现，三重协同纳米平台引发了更强的抗肿瘤免疫反应，包括肿瘤侵袭,细胞因子产生，钙网蛋白易位,和树突状细胞成熟，在体内和体外引发特异性肿瘤特异性免疫反应。使用具有4T1肿瘤的BALB/c小鼠模型来评估体内肿瘤抑制效率，显示B5@HMON组的几乎所有肿瘤在14天后消失。这种简单的无化疗试剂的B5@HMON纳米平台实现了三重协同光免疫疗法。
