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  3. Targeting Peptostreptococcus anaerobius with an Iron-Based Nanozyme Reverses Ferroptosis Resistance and Enhances Antitumor Immunity in Colorectal Cancer

Targeting Peptostreptococcus anaerobius with an Iron-Based Nanozyme Reverses Ferroptosis Resistance and Enhances Antitumor Immunity in Colorectal Cancer

  • Adv Sci (Weinh). 2026 Jan 12:e16272. doi: 10.1002/advs.202516272.
Yinghao Cao 1 2 3 4,  Jun Wang 5 6 7,  Hanwenchen Wang 7,  Xiang Sun 3 4,  Fang Fang 3 4,  Shiying Li 3 4,  Jianping Liu 3 4,  Changrong Shi 3 4,  Pengyuan Qi 2,  Jianhua Zou 3 4,  Xiaoyuan Chen 2 3 4 8 9 10 11 12,  Kailin Cai 7
Affiliations

Affiliations

  • 1 Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 3 Departments of Diagnostic Radiology, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore.
  • 4 Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 5 Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 6 Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 7 Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • 8 Department of Chemical and Biomolecular Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore.
  • 9 Department of Biomedical Engineering, College of Design and Engineering, National University of Singapore, Singapore, Singapore.
  • 10 Department of Pharmacy and Pharmaceutical Sciences, Faculty of Science, National University of Singapore, Singapore, Singapore.
  • 11 Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • 12 Theranostics Center of Excellence (TCE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
PMID: 41524179 DOI: 10.1002/advs.202516272
Abstract

The intratumoral microbiota is a critical determinant of therapeutic outcomes in colorectal Cancer (CRC). Although several microbial species have been identified that influence CRC development and treatment resistance, effective strategies for precisely modulating these bacteria remain limited. In this study, we identify Peptostreptococcus anaerobius as a tumor-enriched anaerobe that promotes CRC progression by inhibiting Ferroptosis. To counteract this, we engineered a composite iron-based nanozyme encapsulating lincomycin, which selectively targets and eradicates intratumoral P. anaerobius, thereby reversing Ferroptosis resistance in CRC. Simultaneously, the nanozyme's inherent peroxidase (POD) like activity catalyzes hydroxyl radical generation, enhancing intracellular oxidative stress and promoting Ferroptosis. This dual mechanism-microbial clearance and ROS-mediated Ferroptosis induction-synergistically suppresses tumor growth. Moreover, ferroptotic Cancer cells release large amounts of damage-associated molecular patterns (DAMPs), which trigger immunogenic cell death (ICD), promoting dendritic cell (DC) maturation and T cell activation, thereby enhancing anti-tumor immunity. Our findings highlight a novel ferroptosis-centered therapeutic strategy integrating microbiota modulation and catalytic nanomedicine for precise CRC treatment.

Keywords

P. anaerobius; colorectal cancer; ferroptosis; immunotherapy; nanozyme.

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