Persistent and Potent Anticancer Immunity Empowered by Manganese-Coordinated STING-Activating Microgels
Jiakun Guo1, Jintao Huang2, Zuliang Huang1, Juan Sun1, Yan Wang1, Hujing Tan1, Di Hu2, Chao Deng(邓超)1*, Xiaoli Zhu(朱晓黎)2*, Zhiyuan Zhong(钟志远)1*
1Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Materials, College of Chemistry, Chemical Engineering and Materials Science, and State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
2Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, China
Adv. Funct. Mater.,2026, 36,e21279
Abstract: Activation of stimulator of interferon genes (STING) pathway represents a powerful strategy to generate potent immune responses for cancer immunotherapy, yet clinical translation is hindered by rapid drug clearance, suboptimal activation, and severe local and systemic toxicity. Herein, we report on manganese-coordinated STING-activating microgels (MSM) for safe, sustained, and synergistic activation of anticancer immunity, effectively annihilating various solid tumors. MSM shows efficient encapsulation (>90%) and gradual release of diABZI agonist and Mn2+ over four weeks, affording cooperative and continuous activation of dendritic cells, MHC upregulation, and proinflammatory cytokine production. Notably, a single intratumoral dose of MSM elicits durable innate and adaptive immunity, remarkably eradicating multiple murine tumors and establishing immune memory against rechallenge. Repurposed as an embolic agent, MSM suppresses orthotopic rabbit VX2 liver tumors and lung metastases through transarterial immunoembolization, demonstrating translational potential across species and tumor models.
Article information: https://doi.org/10.1002/adfm.202521279