Affiliation:
1. Department of Hepatobiliary and Pancreatic Surgery First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China
2. Zhejiang Provincial Key Laboratory of Pancreatic Disease Hangzhou 310003 China
3. College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
4. Innovation Center for the Study of Pancreatic Diseases Hangzhou 310003 China
5. Zhejiang Provincial Clinical Research Center for the Study of Hepatobiliary and Pancreatic Diseases Hangzhou 310003 China
6. Cancer Center Zhejiang University Hangzhou 310058 China
Abstract
AbstractImmunotherapy, 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.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Zhejiang Province
Subject
Pharmaceutical Science,Biomedical Engineering,Biomaterials
Cited by
2 articles.
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