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

doi:10.1039/d3bm00635b

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

Radiology

Research output: Contribution to journal › Article › peer-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 language	English (US)
Pages (from-to)	4652-4663
Number of pages	12
Journal	Biomaterials Science
Volume	11
Issue number	13
DOIs	https://doi.org/10.1039/d3bm00635b
State	Published - May 10 2023

ASJC Scopus subject areas

Materials Science(all)
Biomedical Engineering

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10.1039/d3bm00635b

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@article{6246118169394b7494ec85659a8fafa5,

title = "Multifunctional porous microspheres encapsulating oncolytic bacterial spores and their potential for cancer immunotherapy",

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.",

author = "Bae, {Ga Hyun} and Ryu, {Young Hyun} and Jieun Han and Kim, {Song Hee} and Park, {Chun Gwon} and Park, {Jung Hoon} and Kim, {Dong Hyun} and Chon, {Hong Jae} and Chan Kim and Choi, {Sung Wook} and Wooram Park",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2023 The Royal Society of Chemistry.",

year = "2023",

month = may,

day = "10",

doi = "10.1039/d3bm00635b",

language = "English (US)",

volume = "11",

pages = "4652--4663",

journal = "Biomaterials Science",

issn = "2047-4830",

publisher = "Royal Society of Chemistry",

number = "13",

}

TY - JOUR

T1 - Multifunctional porous microspheres encapsulating oncolytic bacterial spores and their potential for cancer immunotherapy

AU - Bae, Ga Hyun

AU - Ryu, Young Hyun

AU - Han, Jieun

AU - Kim, Song Hee

AU - Park, Chun Gwon

AU - Park, Jung Hoon

AU - Kim, Dong Hyun

AU - Chon, Hong Jae

AU - Kim, Chan

AU - Choi, Sung Wook

AU - Park, Wooram

N1 - Funding Information: 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. Publisher Copyright: © 2023 The Royal Society of Chemistry.

PY - 2023/5/10

Y1 - 2023/5/10

N2 - 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.

AB - 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.

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U2 - 10.1039/d3bm00635b

DO - 10.1039/d3bm00635b

M3 - Article

C2 - 37218418

AN - SCOPUS:85160550626

SN - 2047-4830

VL - 11

SP - 4652

EP - 4663

JO - Biomaterials Science

JF - Biomaterials Science

IS - 13

ER -

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

Abstract

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