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Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy
Abstract
The microbiota in the human gut is strongly correlated with the progression of colorectal cancer (CRC) and with therapeutic responses to CRC. Here, by leveraging the higher concentration of the pro-tumoural Fusobacterium nucleatum and the absence of antineoplastic butyrate-producing bacteria in the faecal microbiota of patients with CRC, we show that-in mice with orthotopic colorectal tumours or with spontaneously formed colorectal tumours-oral or intravenous administration of irinotecan-loaded dextran nanoparticles covalently linked to azide-modified phages that inhibit the growth of F. nucleatum significantly augments the efficiency of first-line chemotherapy treatments of CRC. We also show that oral administration of the phage-guided irinotecan-loaded nanoparticles in piglets led to negligible changes in haemocyte counts, immunoglobulin and histamine levels, and liver and renal functions. Phage-guided nanotechnology for the modulation of the gut microbiota might inspire new approaches for the treatment of CRC.
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“Prebiotics are a group of substances that can be used by host bacteria to enhance the proportion of beneficial species to improve the anti-tumor immunity13–15.”
From Combining gut microbiota modulation and chemotherapy by capecitabine-loaded prebiotic nanoparticle improves colorectal cancer therapy (2023) · cites this paper as [13]
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Metadata
- Authors
- Zheng, D.-W., Dong, X., Pan, P., Chen, K.-W., Fan, J.-X., Cheng, S.-X., & Zhang, X.-Z.
- Affiliations
- Wuhan University (CN)
- Corresponding author
- Zhang, Xian-Zheng
- Venue
- Nature Biomedical Engineering
- Published
- 2019-07-22
- Volume
- 3
- Issue
- 9
- Pages
- 717-728
- ISSN
- 2157-846X (ISSN-L)
- OpenAlex
- W2963121075
- Semantic Scholar
- 94cc03369015ffa0b01be1420acac9b81fce02ac
- Cited by
- 495
- References
- 37
- Citations by year
- 2026: 77 · 2025: 92 · 2024: 96 · 2023: 87 · 2022: 53 · 2021: 45 · 2020: 39 · 2019: 5
- FWCI
- 18.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Biomedical Engineering (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- colorectal cancer, gut microbiota, phage therapy, Fusobacterium nucleatum, irinotecan, dextran nanoparticles, chemotherapy response, butyrate-producing bacteria, orthotopic tumor model, piglet model
- MeSH terms
- Gastrointestinal Microbiome, Irinotecan, Animals, Antineoplastic Agents, Bacteria, Bacteriophages, Butyrates, Colonic Neoplasms, Dextrans, Disease Models, Animal, Drug Therapy, Immunoglobulins, Male, Mice, Inbred C57BL, Colorectal Neoplasms, Fusobacterium nucleatum, Cell Line, Tumor, Cell Proliferation, Mice, Nanoparticles
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