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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: Yang, Kyungmi, Choi, Changhoon, Cho, Hayeong, Ahn, Won-Gyun, Kim, Shin-Yeong, Shin, Sung-Won, Kim, Yeeun, Jang, Taekyu, Lee, Nohyun, Park, Hee Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620922/
https://www.ncbi.nlm.nih.gov/pubmed/34834226
http://dx.doi.org/10.3390/pharmaceutics13111811
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author Yang, Kyungmi
Choi, Changhoon
Cho, Hayeong
Ahn, Won-Gyun
Kim, Shin-Yeong
Shin, Sung-Won
Kim, Yeeun
Jang, Taekyu
Lee, Nohyun
Park, Hee Chul
author_facet Yang, Kyungmi
Choi, Changhoon
Cho, Hayeong
Ahn, Won-Gyun
Kim, Shin-Yeong
Shin, Sung-Won
Kim, Yeeun
Jang, Taekyu
Lee, Nohyun
Park, Hee Chul
author_sort Yang, Kyungmi
collection PubMed
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.
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spelling pubmed-86209222021-11-27 Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models Yang, Kyungmi Choi, Changhoon Cho, Hayeong Ahn, Won-Gyun Kim, Shin-Yeong Shin, Sung-Won Kim, Yeeun Jang, Taekyu Lee, Nohyun Park, Hee Chul Pharmaceutics Article 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. MDPI 2021-10-29 /pmc/articles/PMC8620922/ /pubmed/34834226 http://dx.doi.org/10.3390/pharmaceutics13111811 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Yang, Kyungmi
Choi, Changhoon
Cho, Hayeong
Ahn, Won-Gyun
Kim, Shin-Yeong
Shin, Sung-Won
Kim, Yeeun
Jang, Taekyu
Lee, Nohyun
Park, Hee Chul
Antigen-Capturing Mesoporous Silica Nanoparticles Enhance the Radiation-Induced Abscopal Effect in Murine Hepatocellular Carcinoma Hepa1-6 Models
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620922/
https://www.ncbi.nlm.nih.gov/pubmed/34834226
http://dx.doi.org/10.3390/pharmaceutics13111811
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