Engineering manganese-based immune amplifier for chemoimmunotherapy of peritoneal metastatic colorectal cancer.

Authors

Miaojuan Qiu, Yingfei Wen, Sufen Fang, Tian Hao, Huihui Xu, Xinyi Deng, Takeshi Yamakawa, Binbin Li, Shiqiang Zhang, Yingying Lu, Changhua Zhang, Jing Zhao

Published in

Materials today. Bio. Volume 39. Pages 103376. Epub Jun 23, 2026.

Abstract

Current immunotherapies exhibit limited clinical efficacy in patients with colorectal cancer (CRC). While manganese ions (Mn) can activate the cGAS-STING pathway to potentiate innate immunity, their clinical application is limited by poor tumor accumulation and potential systemic toxicity. Alendronate (ALN), an FDA-approved agent, exerts T cell immunomodulatory activity but is hampered by low bioavailability and undesired bone targeting. To effectively potentiate antitumor immunity against CRC, we developed a manganese-alendronate (MnALN) nanomedicine via infinite coordination, leveraging Mn and ALN to synergistically eliminate tumor cells. In addition, Mn triggers reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress and subsequent immunogenic cell death (ICD) in tumor cells, while its combination with ALN further enhances T cell immune responses, ultimately achieving efficient tumor growth inhibition and intense anti-tumor immune response. This study presented a dual-functional MnALN nanomedicine synthesized from clinically available Mn and ALN, simultaneously activating apoptosis and inflammation-related pathways in CRC cells, which provides an effective strategy for immune tolerance CRC therapy.

PMID:
42404625
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

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