Abstract
Clostridium novyi-NT (C. novyi-NT) is an anaerobic bacterium that can be used for targeted cancer therapy because it germinates selectively in the hypoxic regions of tumor tissues. However, systemic administration of C. novyi-NT spores cannot effectively treat tumors because of the limited intratumoral delivery of active spores. In this study, we demonstrated that multifunctional porous microspheres (MPMs) containing C. novyi-NT spores have the potential for image-guided local tumor therapy. The MPMs can be repositioned under an external magnetic field, enabling precise tumor targeting and retention. Polylactic acid-based MPMs were prepared using the oil-in-water emulsion technique and then coated with a cationic polyethyleneimine polymer prior to loading with negatively charged C. novyi-NT spores. The C. novyi-NT spores delivered by MPMs were released and germinated in a simulated tumor microenvironment, effectively secreting proteins cytotoxic to tumor cells. In addition, the germinated C. novyi-NT induced immunogenic death of the tumor cells and M1 polarization of macrophages. These results indicate that MPMs encapsulated with C. novyi-NT spores have great potential for image-guided cancer immunotherapy.
Original language | English (US) |
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Pages (from-to) | 4652-4663 |
Number of pages | 12 |
Journal | Biomaterials Science |
Volume | 11 |
Issue number | 13 |
DOIs | |
State | Published - May 10 2023 |
Funding
This work was supported by the Korea Medical Device Development Fund grant funded by the Korean government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, the Ministry of Food and Drug Safety) (grant number: 202012D21-02) and a Basic Science Research Program grant (2021R1A2C4001776) through the National Research Foundation of Korea (NRF) grants funded by the Ministry of Science and ICT of the Republic of Korea. All research schemes were created using Biorender.com.
ASJC Scopus subject areas
- Biomedical Engineering
- General Materials Science