Combining augmented radiotherapy and immunotherapy through a nano-gold and bacterial outer-membrane vesicle complex for the treatment of glioblastoma

Mei Hsiu Chen; Tse Ying Liu; Yu Chiao Chen; Ming Hong Chen

doi:10.3390/nano11071661

Combining augmented radiotherapy and immunotherapy through a nano-gold and bacterial outer-membrane vesicle complex for the treatment of glioblastoma

Mei Hsiu Chen, Tse Ying Liu, Yu Chiao Chen, Ming Hong Chen

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-α production.

Original language	English
Article number	1661
Journal	Nanomaterials
Volume	11
Issue number	7
DOIs	https://doi.org/10.3390/nano11071661
Publication status	Published - Jul 2021

Keywords

Glioblastoma
Gold nanoparticles
Immunotherapy
Outer membrane vesicles
Radioenhancer

ASJC Scopus subject areas

General Chemical Engineering
General Materials Science

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10.3390/nano11071661

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title = "Combining augmented radiotherapy and immunotherapy through a nano-gold and bacterial outer-membrane vesicle complex for the treatment of glioblastoma",

abstract = "Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-α production.",

keywords = "Glioblastoma, Gold nanoparticles, Immunotherapy, Outer membrane vesicles, Radioenhancer",

author = "Chen, {Mei Hsiu} and Liu, {Tse Ying} and Chen, {Yu Chiao} and Chen, {Ming Hong}",

note = "Funding Information: Funding: This research was funded by Ministry of Science and Technology, Taiwan, grant number MOST-108-2314-B010-035-MY3; and the Far Eastern Memorial Hospital, grant number FEMH-2020-C-035 and FEMH-2021-C-018. Funding Information: This research was funded by Ministry of Science and Technology, Taiwan, grant number MOST-108-2314-B010-035-MY3; and the Far Eastern Memorial Hospital, grant number FEMH-2020-C-035 and FEMH-2021-C-018. The authors would like to thank Taipei Veterans General Hospital for providing facilities. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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AU - Chen, Mei Hsiu

AU - Liu, Tse Ying

AU - Chen, Yu Chiao

AU - Chen, Ming Hong

N1 - Funding Information: Funding: This research was funded by Ministry of Science and Technology, Taiwan, grant number MOST-108-2314-B010-035-MY3; and the Far Eastern Memorial Hospital, grant number FEMH-2020-C-035 and FEMH-2021-C-018. Funding Information: This research was funded by Ministry of Science and Technology, Taiwan, grant number MOST-108-2314-B010-035-MY3; and the Far Eastern Memorial Hospital, grant number FEMH-2020-C-035 and FEMH-2021-C-018. The authors would like to thank Taipei Veterans General Hospital for providing facilities. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/7

Y1 - 2021/7

N2 - Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-α production.

AB - Glioblastoma, formerly known as glioblastoma multiforme (GBM), is refractory to existing adjuvant chemotherapy and radiotherapy. We successfully synthesized a complex, Au–OMV, with two specific nanoparticles: gold nanoparticles (AuNPs) and outer-membrane vesicles (OMVs) from E. coli. Au–OMV, when combined with radiotherapy, produced radiosensitizing and immuno-modulatory effects that successfully suppressed tumor growth in both subcutaneous G261 tumor-bearing and in situ (brain) tumor-bearing C57BL/6 mice. Longer survival was also noted with in situ tumor-bearing mice treated with Au–OMV and radiotherapy. The mechanisms for the successful treatment were evaluated. Intracellular reactive oxygen species (ROS) greatly increased in response to Au–OMV in combination with radiotherapy in G261 glioma cells. Furthermore, with a co-culture of G261 glioma cells and RAW 264.7 macrophages, we found that GL261 cell viability was related to chemotaxis of macrophages and TNF-α production.

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KW - Radioenhancer

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Combining augmented radiotherapy and immunotherapy through a nano-gold and bacterial outer-membrane vesicle complex for the treatment of glioblastoma

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Keywords

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