2. Academic Validation
  3. Mesoporous manganese nanocarrier target delivery metformin for the co-activation STING pathway to overcome immunotherapy resistance

Mesoporous manganese nanocarrier target delivery metformin for the co-activation STING pathway to overcome immunotherapy resistance

  • iScience. 2024 May 30;27(7):110150. doi: 10.1016/j.isci.2024.110150.
Yuanyao Dou 1 2,  Jie Zheng 2 3,  Jun Kang 2,  Liping Wang 4,  Daijuan Huang 2 3,  Yihui Liu 2,  Chao He 2,  Caiyu Lin 2,  Conghua Lu 2,  Di Wu 2,  Rui Han 2,  Li Li 2,  Liling Tang 1,  Yong He 2 3
Affiliations

Affiliations

  • 1 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China.
  • 2 Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing 400042, China.
  • 3 School of Medicine, Chongqing University, Chongqing 400044, China.
  • 4 Department of pain treatment, the seventh people's Hospital of Chongqing, Chongqing 401320, China.
PMID: 39040065 DOI: 10.1016/j.isci.2024.110150
Abstract

Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to Immune Checkpoint inhibitors in non-small cell lung Cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use. Here, we constructed high-mesoporous Mn-based nanocarrier loading metformin nanoparticles (Mn-MSN@Met-M NPs) that actively target tumors and respond to release higher concentration of Mn2+ ions and metformin. The NPs significantly enhanced the T cells to kill lung Cancer cells with the STK11 mutant. The mechanism shows that enhanced STING pathway activation promotes STING, TBKI, and IRF3 phosphorylation through Mn2+ ions and metformin release from NPs, thus boosting type I interferon production. In vivo, NPs in combination with a PD-1 inhibitor effectively decreased tumor growth. Collectively, we developed a Mn-MSN@Met-M nanoactivator to intensify immune activation for potential Cancer Immunotherapy.

Keywords

Biomaterials; Drug delivery system.

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