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Engineered multitargeting exosomes carrying miR-323a-3p for CRC therapy
Yechun Pang1, Xingshi Chen2, Baiying Xu3
1Department of General Surgery, Pudong New Area People's Hospital, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
International Journal of Biological Macromolecules
|July 13, 2023
Summary
Engineered exosomes loaded with miR-323a-3p (miR-Exo) target EGFR and TYMS, inhibiting colorectal cancer (CRC) growth and enhancing 5-Fluorouracil (5-FU) chemotherapy effectiveness.
Area of Science:
- Oncology
- Molecular Biology
- Nanomedicine
Background:
- Colorectal cancer (CRC) presents high incidence and mortality, with 5-Fluorouracil (5-FU) as a primary treatment.
- Chemoresistance and systemic side effects limit 5-FU efficacy, necessitating improved therapeutic strategies.
Purpose of the Study:
- To develop engineered exosomes (miR-Exo) overexpressing miR-323a-3p for enhanced CRC treatment.
- To investigate the therapeutic potential of miR-Exo in targeting EGFR and TYMS in CRC.
Main Methods:
- CRC cells engineered to overexpress miR-323a-3p.
- Isolation and purification of miR-323a-3p-loaded exosomes (miR-Exo).
- Evaluation of miR-Exo efficacy in cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models.
Main Results:
- miR-Exo significantly inhibited CRC cell proliferation and induced apoptosis by targeting EGFR.
- miR-Exo reversed 5-FU resistance by inhibiting TYMS upregulation.
- Tumor regression observed in CDX and PDX models, with enhanced 5-FU therapeutic effects.
Conclusions:
- miR-Exo effectively induces CRC cell apoptosis via EGFR and TYMS targeting.
- miR-Exo enhances the therapeutic efficacy of 5-FU in colorectal cancer.
- miR-Exo shows promise as a biotherapy for advanced CRC.
