有效的抗癌免疫取决于正确激活癌症免疫循环中的多个逐步事件。免疫学上的“冷”肿瘤微环境（TME）会导致免疫逃避和传统检查点阻断免疫疗法的无效性。在这里，我们将纳米颗粒制剂和原位形成的水凝胶支架结合起来，局部治疗可触及的肿瘤，并刺激针对转移性肿瘤病变的全身免疫力。纳米颗粒通过活性氧 (ROS) 可裂解连接体封装聚（ε-己内酯）衍生的细胞毒性化疗药物和 Toll 样受体 7/8 佐剂，该连接体可在近红外光照射后被共组装的相邻光敏剂自激活。 NIR）激光照射。进一步的开发产生了可注射的、近红外光响应的、免疫原性的水凝胶（iGEL），它可以植入肿瘤周围并沉积到肿瘤手术床上。在近红外激光照射下，产生的 ROS 会诱导聚合物-药物缀合物中的 iGEL 降解和键断裂，引发癌细胞中的免疫原性细胞死亡级联，并自发释放封装的试剂以重新连接癌症-免疫循环。值得注意的是，在黑色素瘤和三阴性乳腺癌的多种临床前模型中的应用（这些模型具有侵袭性且对传统免疫疗法难以治疗），iGEL 可以诱导已形成肿瘤的持久缓解，延长术后无肿瘤生存期，并抑制转移负担。这项研究的结果是一种可局部给药的免疫原性水凝胶，用于触发宿主全身免疫，以提高免疫治疗效果，同时将脱靶副作用降至最低。

Effective anticancer immunity depends on properly activating multiple stepwise events in the cancer-immunity cycle. An immunologically "cold" tumor microenvironment (TME) engenders immune evasion and refractoriness to conventional checkpoint blockade immunotherapy. Here, we combine nanoparticle formulations and an in situ formed hydrogel scaffold to treat accessible tumors locally and to stimulate systemic immunity against metastatic tumor lesions. The nanoparticles encapsulate poly(ε-caprolactone)-derived cytotoxic chemotherapy and adjuvant of Toll-like receptor 7/8 through a reactive oxygen species (ROS)-cleavable linker that can be self-activated by the coassembled neighboring photosensitizer following near-infrared (NIR) laser irradiation. Further development results in syringeable, NIR light-responsive, and immunogenic hydrogel (iGEL) that can be implanted peritumorally and deposited into the tumor surgical bed. Upon NIR laser irradiation, the generated ROS induces iGEL degradation and bond cleavage in the polymer-drug conjugates, triggering the immunogenic cell death cascade in cancer cells and spontaneously releasing encapsulated agents to rewire the cancer-immunity cycle. Notably, upon application in multiple preclinical models of melanoma and triple-negative breast cancer, which are aggressive and refractory to conventional immunotherapy, iGEL induces durable remission of established tumors, extends postsurgical tumor-free survival, and inhibits metastatic burden. The result of this study is a locally administrable immunogenic hydrogel for triggering host systemic immunity to improve immunotherapeutic efficacy with minimal off-target side effects.