Shenzhen Children's Hospital, Clinical Medical College of Shenzhen University, Shenzhen University, Shenzhen, 518060, PR China; Academy of Medical Engineering and Translational Medicine, Medical College, Tianjin University, Tianjin 300072, PR China; International Joint Research Center for Molecular Science, College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, 518060, PR China.
Shenzhen Eye Hospital, Jinan University, Shenzhen Eye Institute, Shenzhen, 518040, PR China.
Biomaterials. 2024 Dec;311:122696. doi: 10.1016/j.biomaterials.2024.122696. Epub 2024 Jul 2.
Cancer immunotherapy has been developed to improve therapeutic effects for patients by activating the innate immune stimulator of interferon gene (STING) pathway. However, most patients cannot benefit from this therapy, mainly due to the problems of excessively low immune responses and lack of tumor specificity. Herein, we report a solution to these two problems by developing a bifunctional platform of black phosphorus quantum dots (BPQDs) for STING agonists. Specifically, BPQDs could connect targeted functional groups and regulate surface zeta potential by coordinating metal ions to increase loading (over 5 times) while maintaining high universality (7 STING agonists). The controlled release of STING agonists enabled specific interactions with their proteins, activating the STING pathway and stimulating the secretion release of immunosuppressive factors by phosphorylating TBK1 and IFN-IRF3 and secreting high levels of immunostimulatory cytokines, including IL-6, IFN-α, and IFN-β. Moreover, the immunotherapy was enhanced was enhanced mild photothermal therapy (PTT) of BPQDs platform, producing enough T cells to eliminate tumors and prevent tumor recurrence. This work facilitates further research on targeted delivery of small-molecule immune drugs to enhance the development of clinical immunotherapy.
癌症免疫疗法的发展旨在通过激活干扰素基因（STING）途径的先天免疫刺激物来提高患者的治疗效果。然而，大多数患者无法从这种治疗中受益，主要是由于免疫反应过低和缺乏肿瘤特异性这两个问题。在此，我们通过开发用于 STING 激动剂的黑磷量子点（BPQDs）双功能平台来解决这两个问题。具体而言，BPQDs 可以通过协调金属离子连接靶向功能基团并调节表面 zeta 电位来增加负载（超过 5 倍），同时保持高度通用性（7 种 STING 激动剂）。STING 激动剂的控制释放使其能够与蛋白质进行特异性相互作用，通过磷酸化 TBK1 和 IFN-IRF3 激活 STING 途径，并分泌高水平的免疫刺激性细胞因子，包括 IL-6、IFN-α 和 IFN-β。此外，BPQDs 平台的温和光热疗法（PTT）增强了免疫治疗，产生了足够的 T 细胞来消除肿瘤并防止肿瘤复发。这项工作促进了针对小分子免疫药物的靶向递送的进一步研究，以增强临床免疫疗法的发展。
