Multifunctional porous microspheres encapsulating oncolytic bacterial spores and their potential for cancer immunotherapy

Ga Hyun Bae, Young Hyun Ryu, Jieun Han, Song Hee Kim, Chun Gwon Park, Jung Hoon Park, Dong Hyun Kim, Hong Jae Chon, Chan Kim, Sung Wook Choi*, Wooram Park*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)4652-4663
Number of pages12
JournalBiomaterials Science
Volume11
Issue number13
DOIs
StatePublished - May 10 2023

ASJC Scopus subject areas

  • Materials Science(all)
  • Biomedical Engineering

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