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Magnetic natural lipid nanoparticles for oral treatment of colorectal cancer through potentiated antitumor immunity and microbiota metabolite regulation
Open accessAbstract
The therapeutic efficacy of oral nanotherapeutics against colorectal cancer (CRC) is restricted by inadequate drug accumulation, immunosuppressive microenvironment, and intestinal microbiota imbalance. To overcome these challenges, we elaborately constructed 6-gingerol (Gin)-loaded magnetic mesoporous silicon nanoparticles and functionalized their surface with mulberry leaf-extracted lipids (MLLs) and Pluronic F127 (P127). In vitro experiments revealed that P127 functionalization and alternating magnetic fields (AMFs) promoted internalization of the obtained P127-MLL@Gins by colorectal tumor cells and induced their apoptosis/ferroptosis through Gin/ferrous ion-induced oxidative stress and magneto-thermal effect. After oral administration, P127-MLL@Gins safely passed to the colorectal lumen, infiltrated the mucus barrier, and penetrated into the deep tumors under the influence of AMFs. Subsequently, the P127-MLL@Gin (+ AMF) treatment activated antitumor immunity and suppressed tumor growth. We also found that this therapeutic modality significantly increased the abundance of beneficial bacteria (e.g., Bacillus and unclassified-c-Bacilli), reduced the proportions of harmful bacteria (e.g., Bacteroides and Alloprevotella), and increased lipid oxidation metabolites. Strikingly, checkpoint blockers synergistically improved the therapeutic outcomes of P127-MLL@Gins (+ AMF) against orthotopic and distant colorectal tumors and significantly prolonged mouse life spans. Overall, this oral therapeutic platform is a promising modality for synergistic treatment of CRC.
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Metadata
- Authors
- Li, B., Zu, M., Jiang, A., Cao, Y., Wu, J., Shahbazi, M.-A., Shi, X., Reis, R. L., Kundu, S. C., & Xiao, B.
- Affiliations
- Southwest University (CN)
- University Medical Center Groningen (NL)
- 3B's Research Group (PT)
- Corresponding author
- Shi, Xiaoxiao
- Xiao, Bo
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2024-06
- Volume
- 307
- Pages
- 122530
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W4392639059
- Semantic Scholar
- 7dc66ae35e57450b93641f1fd2d4b08ed3e12c58
- Cited by
- 67
- References
- 54
- Citations by year
- 2026: 27 · 2025: 27 · 2024: 13
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- green
- research.rug.nl
- Licence
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China
- Venture and Innovation Support Program for Chongqing Overseas Returnees
- Fundamental Research Funds for the Central Universities
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Keywords
- colorectal cancer, 6-gingerol, alternating magnetic field, Pluronic F127, ferroptosis, oxidative stress, tumor microenvironment, antitumor immunity, gut microbiota, immune checkpoint blockade
- MeSH terms
- Gastrointestinal Microbiome, Administration, Oral, Animals, Liposomes, Colorectal Neoplasms, Mice, Nanoparticles, Tumor Microenvironment, Magnetic Phenomena
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