Engineered GLUT1-targeted STING polyproagonists: Redox-triggered activation and enhanced endosomal escape for cancer immunotherapy
Arsalan RazaDepartment of Polymer Science and Engineering, University of Science and Technology of China, Hefei 230026, ChinaAnum KayaniSchool of Chemistry, Xi'an Key Laboratory of Sustainable Polymer Materials, Xi'an Jiaotong University, Xi'an 710049, ChinaGuopu HuangSchool of Chemistry, Xi'an Key Laboratory of Sustainable Polymer Materials, Xi'an Jiaotong University, Xi'an 710049, ChinaCheng LiDepartment of Geriatric General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, ChinaQinghao ZhouSchool of Chemistry, Xi'an Key Laboratory of Sustainable Polymer Materials, Xi'an Jiaotong University, Xi'an 710049, ChinaKhurshed BozorovDepartment of Organic Synthesis and Bioorganic Chemistry, Institute of Biochemistry, Samarkand State University, Samarkand 140104, UzbekistanYuanyuan JiDepartment of Geriatric General Surgery, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, ChinaZhishen GeSchool of Chemistry, Xi'an Key Laboratory of Sustainable Polymer Materials, Xi'an Jiaotong University, Xi'an 710049, China
2026en
ABI
Abstract
-BMA) segments promote endosomal escape, followed by the release of the disulfide-linked SR-717 in the cytosol under reducing conditions. This leads to robust activation of the STING pathway, resulting in dendritic cell maturation, enhanced T-cell infiltration, and potent antitumor immunity. Furthermore, when combined with an αPD-L1, this polyproagonist synergistically enhances the efficacy of immune checkpoint blockade, effectively inhibiting primary and distant tumors by counteracting immune evasion. This study highlights the potential of STING polyproagonists in achieving effective cytosolic delivery of STING agonists to boost antitumor immunity and overcome current limitations associated with STING immunotherapy.
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