Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models

Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the ab...

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Autores principales:	Kyungmi Yang, Changhoon Choi, Hayeong Cho, Won-Gyun Ahn, Shin-Yeong Kim, Sung-Won Shin, Yeeun Kim, Taekyu Jang, Nohyun Lee, Hee Chul Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mesoporous silica nanoparticles radiotherapy immunotherapy tumor microenvironment abscopal effect Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/ad7a455232484d50ab02c2fd50826ad4
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spelling	oai:doaj.org-article:ad7a455232484d50ab02c2fd50826ad42021-11-25T18:40:51ZAntigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models10.3390/pharmaceutics131118111999-4923https://doaj.org/article/ad7a455232484d50ab02c2fd50826ad42021-10-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1811https://doaj.org/toc/1999-4923Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT.Kyungmi YangChanghoon ChoiHayeong ChoWon-Gyun AhnShin-Yeong KimSung-Won ShinYeeun KimTaekyu JangNohyun LeeHee Chul ParkMDPI AGarticlemesoporous silica nanoparticlesradiotherapyimmunotherapytumor microenvironmentabscopal effectPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1811, p 1811 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mesoporous silica nanoparticles radiotherapy immunotherapy tumor microenvironment abscopal effect Pharmacy and materia medica RS1-441
spellingShingle	mesoporous silica nanoparticles radiotherapy immunotherapy tumor microenvironment abscopal effect Pharmacy and materia medica RS1-441 Kyungmi Yang Changhoon Choi Hayeong Cho Won-Gyun Ahn Shin-Yeong Kim Sung-Won Shin Yeeun Kim Taekyu Jang Nohyun Lee Hee Chul Park Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
description	Immunomodulation by radiotherapy (RT) is an emerging strategy for improving cancer immunotherapy. Nanomaterials have been employed as innovative tools for cancer therapy. This study aimed to investigate whether mesoporous silica nanoparticles (MSNs) enhance RT-mediated local tumor control and the abscopal effect by stimulating anti-cancer immunity. Hepa1-6 murine hepatocellular carcinoma syngeneic models and immunophenotyping with flow cytometry were used to evaluate the immune responses. When mice harboring bilateral tumors received 8 Gy of X-rays on a single tumor, the direct injection of MSNs into irradiated tumors enhanced the growth inhibition of irradiated and unirradiated contralateral tumors. MSNs enhanced RT-induced tumor infiltration of cytotoxic T cells on both sides and suppressed RT-enhanced infiltration of regulatory T cells. The administration of MSNs pre-incubated with irradiated cell-conditioned medium enhanced the anti-tumor effect of anti-PD1 compared to the as-synthesized MSNs. Intracellular uptake of MSNs activated JAWS II dendritic cells (DCs), which were consistently observed in DCs in tumor-draining lymph nodes (TDLNs). Our findings suggest that MSNs may capture tumor antigens released after RT, which is followed by DC maturation in TDLNs and infiltration of cytotoxic T cells in tumors, thereby leading to systemic tumor regression. Our results suggest that MSNs can be applied as an adjuvant for in situ cancer vaccines with RT.
format	article
author	Kyungmi Yang Changhoon Choi Hayeong Cho Won-Gyun Ahn Shin-Yeong Kim Sung-Won Shin Yeeun Kim Taekyu Jang Nohyun Lee Hee Chul Park
author_facet	Kyungmi Yang Changhoon Choi Hayeong Cho Won-Gyun Ahn Shin-Yeong Kim Sung-Won Shin Yeeun Kim Taekyu Jang Nohyun Lee Hee Chul Park
author_sort	Kyungmi Yang
title	Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title_short	Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title_full	Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title_fullStr	Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title_full_unstemmed	Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title_sort	antigen-capturing mesoporous silica nanoparticles enhance the radiation-induced abscopal effect in murine hepatocellular carcinoma hepa1-6 models
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ad7a455232484d50ab02c2fd50826ad4
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Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models

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