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Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer
The development of an optimal treatment modality to improve the therapeutic outcome of breast cancer patients is still difficult. Poor antigen presentation to T cells is a major challenge in cancer immunotherapy. In this study, a synergistic immunotherapy strategy for breast cancer incorporating imm...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487313/ https://www.ncbi.nlm.nih.gov/pubmed/37693071 http://dx.doi.org/10.1002/btm2.10379 |
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author | Banstola, Asmita Pandit, Mahesh Duwa, Ramesh Chang, Jae‐Hoon Jeong, Jee‐Heon Yook, Simmyung |
author_facet | Banstola, Asmita Pandit, Mahesh Duwa, Ramesh Chang, Jae‐Hoon Jeong, Jee‐Heon Yook, Simmyung |
author_sort | Banstola, Asmita |
collection | PubMed |
description | The development of an optimal treatment modality to improve the therapeutic outcome of breast cancer patients is still difficult. Poor antigen presentation to T cells is a major challenge in cancer immunotherapy. In this study, a synergistic immunotherapy strategy for breast cancer incorporating immune cell infiltration, immunogenic cell death (ICD), and dendritic cell (DC) maturation through a reactive oxygen species (ROS)‐responsive dual‐targeted smart nanosystem (anti‐PD‐L1‐TKNP) for the simultaneous release of DOX, R848, and MIP‐3α in the tumor microenvironment is reported. Following local injection, anti‐PD‐L1‐DOX‐R848‐MIP‐3α/thioketal nanoparticle (TKNP) converts tumor cells to a vaccine owing to the combinatorial effect of DOX‐induced ICD, R848‐mediated immunostimulatory properties, and MIP‐3α‐induced immune cell recruitment in the tumor microenvironment. Intratumoral injection of anti‐PD‐L1‐DOX‐R848‐MIP‐3α/TKNP caused significant regression of breast cancer. Mechanistic studies reveal that anti‐PD‐L1‐DOX‐R848‐MIP‐3α/TKNP specifically targets tumor tissue, resulting in maximum exposure of calreticulin (CRT) and HMGB1 in tumors, and significantly enhances intratumoral infiltration of CD4(+) and CD8(+) T cells in tumors. Therefore, a combined strategy using dual‐targeted ROS‐responsive TKNP highlights the significant application of nanoparticles in modulating the tumor microenvironment and could be a clinical treatment strategy for effective breast cancer management. |
format | Online Article Text |
id | pubmed-10487313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104873132023-09-09 Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer Banstola, Asmita Pandit, Mahesh Duwa, Ramesh Chang, Jae‐Hoon Jeong, Jee‐Heon Yook, Simmyung Bioeng Transl Med Special Issue Articles The development of an optimal treatment modality to improve the therapeutic outcome of breast cancer patients is still difficult. Poor antigen presentation to T cells is a major challenge in cancer immunotherapy. In this study, a synergistic immunotherapy strategy for breast cancer incorporating immune cell infiltration, immunogenic cell death (ICD), and dendritic cell (DC) maturation through a reactive oxygen species (ROS)‐responsive dual‐targeted smart nanosystem (anti‐PD‐L1‐TKNP) for the simultaneous release of DOX, R848, and MIP‐3α in the tumor microenvironment is reported. Following local injection, anti‐PD‐L1‐DOX‐R848‐MIP‐3α/thioketal nanoparticle (TKNP) converts tumor cells to a vaccine owing to the combinatorial effect of DOX‐induced ICD, R848‐mediated immunostimulatory properties, and MIP‐3α‐induced immune cell recruitment in the tumor microenvironment. Intratumoral injection of anti‐PD‐L1‐DOX‐R848‐MIP‐3α/TKNP caused significant regression of breast cancer. Mechanistic studies reveal that anti‐PD‐L1‐DOX‐R848‐MIP‐3α/TKNP specifically targets tumor tissue, resulting in maximum exposure of calreticulin (CRT) and HMGB1 in tumors, and significantly enhances intratumoral infiltration of CD4(+) and CD8(+) T cells in tumors. Therefore, a combined strategy using dual‐targeted ROS‐responsive TKNP highlights the significant application of nanoparticles in modulating the tumor microenvironment and could be a clinical treatment strategy for effective breast cancer management. John Wiley & Sons, Inc. 2022-08-03 /pmc/articles/PMC10487313/ /pubmed/37693071 http://dx.doi.org/10.1002/btm2.10379 Text en © 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of The American Institute of Chemical Engineers. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Special Issue Articles Banstola, Asmita Pandit, Mahesh Duwa, Ramesh Chang, Jae‐Hoon Jeong, Jee‐Heon Yook, Simmyung Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title | Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title_full | Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title_fullStr | Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title_full_unstemmed | Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title_short | Reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
title_sort | reactive oxygen species‐responsive dual‐targeted nanosystem promoted immunogenic cell death against breast cancer |
topic | Special Issue Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10487313/ https://www.ncbi.nlm.nih.gov/pubmed/37693071 http://dx.doi.org/10.1002/btm2.10379 |
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