Department of Laboratory Medicine, Dongguan Institute of Clinical Cancer Research, Affiliated Dongguan Hospital, Southern Medical University, Dongguan, 523018, China.
School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou, 510515, China.
Adv Mater. 2023 Nov;35(48):e2303149. doi: 10.1002/adma.202303149. Epub 2023 Oct 27.
Pharmacological activation of the stimulator of interferon genes (STING) pathway has become a promising strategy for cancer immunotherapy. However, the insufficient tumorous accumulation, rapid clearance, and short duration of drug efficacy in the tumor microenvironment of small structural STING agonists greatly compromise the therapeutic efficacy. Herein, a tumorous extracellular matrix (ECM) is presented anchoring STING agonist-based photoimmunothernostic nanomedicine (SAPTN) that can be activated by mild-temperature photothermal therapy (mild PTT) induced neutrophilic inflammation. The SAPTN owns second window near-infrared (NIR-II) photonics properties fitting for NIR-II fluorescence and photoacoustic imaging-guided cancer therapy. The aggregates SAPTN targeting to the ECM provide slow and continuous release of potent STING agonists diABZIs. The mild PTT and long-lasting STING agonists released in the ECM synergistically prime systematic, robust, and long-term anticancer immunity. In a tumor model, this approach leads to complete tumor eradication in about 100% of mice with orthotopic breast tumors, and the mice regained tumor-free survival of at least 2 months. In addition, the immune-mediated abscopal effect shows inhibition of the distant solid tumor growth by intratumoral administration of SAPTN with laser irradiation. Overall, this approach represents a generalized photoactivable nanomedicine to prime anticancer immunity for improved cancer theranostics.
激动干扰素基因刺激物（STING）通路的药理学激活已成为癌症免疫治疗的一种有前途的策略。然而，小结构 STING 激动剂在肿瘤微环境中的肿瘤积累不足、快速清除和药效持续时间短，极大地影响了治疗效果。在此，提出了一种基于肿瘤细胞外基质（ECM）锚定的 STING 激动剂光免疫治疗纳米药物（SAPTN），该药物可被温和温度光热疗法（mild PTT）诱导的嗜中性粒细胞炎症激活。SAPTN 具有适合近红外二区（NIR-II）荧光和光声成像引导癌症治疗的第二近红外窗口光子特性。靶向 ECM 的 SAPTN 聚集物提供了强效 STING 激动剂 diABZIs 的缓慢持续释放。温和 PTT 和在 ECM 中释放的长效 STING 激动剂协同引发系统、强大和长期的抗癌免疫。在肿瘤模型中，这种方法导致约 100%患有原位乳腺癌的小鼠完全消除肿瘤，并且小鼠至少有 2 个月的无肿瘤存活期。此外，免疫介导的远隔效应表明，通过肿瘤内给予 SAPTN 并进行激光照射，可抑制远处实体瘤的生长。总的来说，这种方法代表了一种通用的光激活纳米医学方法，可用于引发抗癌免疫，以改善癌症治疗。
