In Situ Formed ROS‐Responsive Hydrogel with STING Agonist and Gemcitabine to Intensify Immunotherapy against Pancreatic Ductal Adenocarcinoma
In Situ Formed ROS‐Responsive Hydrogel with STING Agonist and Gemcitabine to Intensify Immunotherapy against Pancreatic Ductal Adenocarcinoma
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使用 STING 激动剂和吉西他滨原位形成 ROS 响应水凝胶，强化胰腺导管腺癌的免疫治疗
DOI：
10.1002/adhm.202203264
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发表时间：
2023
影响因子：
10
通讯作者：
T. Liang
中科院分区：
文献类型：
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作者：
Meng Wang;Qi;Junming Huang;Fu;Zhu Yao;S. Shao;Xinyu Zhao;T. Liang
免疫疗法是最具革命性的抗癌策略，但由于高度免疫抑制的肿瘤微环境（TME），在胰腺导管腺癌（PDAC）中取得理想结果面临着重大障碍。同时，单独使用PDAC治疗中的传统一线化疗药物吉西他滨（GEM）也不足以达到持久疗效。在这项研究中，活性氧可降解水凝胶系统（称为 GEM-STING@Gel）被设计用于将吉西他滨和干扰素基因刺激剂 (STING) 激动剂 DMXAA（5,6-二甲基呫吨酮-4-乙酸）共同输送到肿瘤部位。在这项工作中，该策略通过一个简单的平台解决了当前免疫疗法的主要挑战，该平台可以协同激活先天免疫并促进肿瘤部位的细胞毒性T淋巴细胞浸润，从而调节免疫抑制性TME。此外，免疫疗法的有效治疗效力在原位术后模型中得到证实，释放了预防手术切除后肿瘤复发的转化潜力。这项研究强调了这种结合化疗、免疫疗法和生物材料水凝胶的综合策略的优势，包括提高治疗效果、操作便利性和卓越的生物安全性。
Immunotherapy, the most revolutionary anticancer strategy, faces major obstacles in yielding desirable outcomes in pancreatic ductal adenocarcinoma (PDAC) due to the highly immunosuppressive tumor microenvironment (TME). Meanwhile, when used alone, the traditional first‐line chemotherapeutic agent gemcitabine (GEM) in PDAC treatment is also insufficient to achieve lasting efficacy. In this study, a reactive oxygen species degradable hydrogel system, denoted as GEM‐STING@Gel, is engineered to codeliver gemcitabine and the stimulator of interferon genes (STING) agonist DMXAA (5,6‐dimethylxanthenone‐4‐acetic acid) into the tumor site. In this work, the strategy addresses the major challenges of current immunotherapies with a facile platform, which can synergistically activate innate immunity and promote the cytotoxic T lymphocytes infiltration at the tumor site, thereby modulating the immunosuppressive TME. Further, the efficient therapeutic potency of the immunotherapy is confirmed in an orthotopic postsurgical model, unleashing the translational potential to prevent tumor recurrence after surgical resection. This study underscores the advantages of this integrative strategy that combines chemotherapy, immunotherapy, and biomaterial‐based hydrogel, including improved therapeutic efficacy, operational convenience, and superior biosafety.
DOI：
--
发表时间：
2011
期刊：
影响因子：
--
作者：
Sumimoto H;Minakami R;Miyano K
通讯作者：
Miyano K