A Single‐Atom Mn/MoO 3− x Nanoagonist for Cascade cGAS/STING Activation in Tumor‐Specific Catalytic Metalloimmunotherapy
Source abstract
Abstract
Abstract The cyclic GMP‐AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway plays a crucial role in initiating anti‐tumor immunity. Despite the development of various STING agonists, their effectiveness is often limited by suboptimal activation efficiency and poor sustainability. To address this, a Mn/MoO 3− x nanoagonist featuring Mn single‐atom sites is presented, designed for cascade cGAS/STING activation in tumor‐specific catalytic metalloimmunotherapy. The single‐atom nanoagonist (SANA) is meticulously crafted by doping Mn atoms into defective molybdenum oxide (MoO 3− x ), enabling robust peroxidase‐mimicking catalysis and inducing severe double‐stranded DNA (dsDNA) damage in tumors. Of note, Mn 2+ and MoO 4 2− can be responsively released from Mn/MoO 3− x SANA and enhance the sensitivity of cGAS to dsDNA. Importantly, MoO 4 2− with a relatively slow‐release profile and facile cellular accumulation compensates for Mn 2+ that has poor cellular accumulation due to continuous efflux, thus continuatively triggering the secretion of type I interferon for beyond 72 h. Remarkably, Mn/MoO 3− x SANA significantly inhibits tumor growth and metastasis without supplementary STING agonists or external stimulation. This study offers a promising cascade cGAS/STING activation approach to enhance the efficacy and sustainability of catalytic metalloimmunotherapy.
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Research context
OpenAlex topics: Advanced Nanomaterials in Catalysis · Nanoplatforms for cancer theranostics · interferon and immune responses
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Pharmacy Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application Anhui University of Chinese Medicine Hefei Anhui 230038 China
Institute of Pharmaceutics Anhui Academy of Chinese Medicine Hefei Anhui 230038 China
Institute of Pharmaceutics Hangzhou Institute of Innovative Medicine College of Pharmaceutical Sciences Zhejiang University Hangzhou 310058 China
Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical Engineering National Center for Translational Medicine Shanghai Jiao Tong University Shanghai 200240 China
WLA Laboratories Shanghai 201203 China
Department of Clinical Laboratory, Songjiang Research Institute Shanghai Key Laboratory of Emotions and Affective Disorders (LEAD) Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Shanghai 201600 China
Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009 China
School of Chemistry and Chemical Engineering Hefei University of Technology Hefei Anhui 230009 China
Funding
National Key Research and Development Program of China · National Natural Science Foundation of China
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