癌症免疫疗法已被开发出来，通过激活干扰素基因的先天免疫刺激剂（STING）途径来提高患者的治疗效果。然而，大多数患者无法从这种疗法中获益，主要是由于免疫反应过低和缺乏肿瘤特异性的问题。在此，我们通过开发用于 STING 激动剂的黑磷量子点（BPQD）双功能平台来解决这两个问题。具体来说，BPQD 可以连接目标官能团，并通过协调金属离子来增加负载量（超过 5 倍）来调节表面 zeta 电位，同时保持高通用性（7 种 STING 激动剂）。 STING 激动剂的受控释放能够与其蛋白质发生特异性相互作用，激活 STING 通路并通过磷酸化 TBK1 和 IFN-IRF3 刺激免疫抑制因子的分泌释放，并分泌高水平的免疫刺激细胞因子，包括 IL-6、IFN-α 和干扰素-β。此外，免疫疗法得到增强，BPQDs平台增强了温和光热疗法（PTT），产生足够的T细胞来消除肿瘤并防止肿瘤复发。这项工作有助于进一步研究小分子免疫药物的靶向递送，以促进临床免疫治疗的发展。版权所有 © 2024 Elsevier Ltd. 保留所有权利。

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.Copyright © 2024 Elsevier Ltd. All rights reserved.