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Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses

Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the con...

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Autores principales: Kim, Jeongrae, Choi, Yongwhan, Yang, Suah, Lee, Jaewan, Choi, Jiwoong, Moon, Yujeong, Kim, Jinseong, Shim, Nayeon, Cho, Hanhee, Shim, Man Kyu, Jeon, Sangmin, Lim, Dong-Kwon, Yoon, Hong Yeol, Kim, Kwangmeyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954063/
https://www.ncbi.nlm.nih.gov/pubmed/35335852
http://dx.doi.org/10.3390/pharmaceutics14030474
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author Kim, Jeongrae
Choi, Yongwhan
Yang, Suah
Lee, Jaewan
Choi, Jiwoong
Moon, Yujeong
Kim, Jinseong
Shim, Nayeon
Cho, Hanhee
Shim, Man Kyu
Jeon, Sangmin
Lim, Dong-Kwon
Yoon, Hong Yeol
Kim, Kwangmeyung
author_facet Kim, Jeongrae
Choi, Yongwhan
Yang, Suah
Lee, Jaewan
Choi, Jiwoong
Moon, Yujeong
Kim, Jinseong
Shim, Nayeon
Cho, Hanhee
Shim, Man Kyu
Jeon, Sangmin
Lim, Dong-Kwon
Yoon, Hong Yeol
Kim, Kwangmeyung
author_sort Kim, Jeongrae
collection PubMed
description Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 °C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities.
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spelling pubmed-89540632022-03-26 Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses Kim, Jeongrae Choi, Yongwhan Yang, Suah Lee, Jaewan Choi, Jiwoong Moon, Yujeong Kim, Jinseong Shim, Nayeon Cho, Hanhee Shim, Man Kyu Jeon, Sangmin Lim, Dong-Kwon Yoon, Hong Yeol Kim, Kwangmeyung Pharmaceutics Article Immunogenic cell death (ICD) is a powerful trigger eliciting strong immune responses against tumors. However, traditional chemoimmunotherapy (CIT) does not last long enough to induce sufficient ICD, and also does not guarantee the safety of chemotherapeutics. To overcome the disadvantages of the conventional approach, we used doxorubicin (DOX) as an ICD inducer, and poly(lactic-co-glycolic acid) (PLGA)-based nanomedicine platform for controlled release of DOX. The diameter of 138.7 nm of DOX-loaded PLGA nanoparticles (DP-NPs) were stable for 14 days in phosphate-buffered saline (PBS, pH 7.4) at 37 °C. Furthermore, DOX was continuously released for 14 days, successfully inducing ICD and reducing cell viability in vitro. Directly injected DP-NPs enabled the remaining of DOX in the tumor site for 14 days. In addition, repeated local treatment of DP-NPs actually lasted long enough to maintain the enhanced antitumor immunity, leading to increased tumor growth inhibition with minimal toxicities. Notably, DP-NPs treated tumor tissues showed significantly increased maturated dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) population, showing enhanced antitumor immune responses. Finally, the therapeutic efficacy of DP-NPs was maximized in combination with an anti-programmed death-ligand 1 (PD-L1) antibody (Ab). Therefore, we expect therapeutic efficacies of cancer CIT can be maximized by the combination of DP-NPs with immune checkpoint blockade (ICB) by achieving proper therapeutic window and continuously inducing ICD, with minimal toxicities. MDPI 2022-02-22 /pmc/articles/PMC8954063/ /pubmed/35335852 http://dx.doi.org/10.3390/pharmaceutics14030474 Text en © 2022 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
Kim, Jeongrae
Choi, Yongwhan
Yang, Suah
Lee, Jaewan
Choi, Jiwoong
Moon, Yujeong
Kim, Jinseong
Shim, Nayeon
Cho, Hanhee
Shim, Man Kyu
Jeon, Sangmin
Lim, Dong-Kwon
Yoon, Hong Yeol
Kim, Kwangmeyung
Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title_full Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title_fullStr Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title_full_unstemmed Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title_short Sustained and Long-Term Release of Doxorubicin from PLGA Nanoparticles for Eliciting Anti-Tumor Immune Responses
title_sort sustained and long-term release of doxorubicin from plga nanoparticles for eliciting anti-tumor immune responses
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8954063/
https://www.ncbi.nlm.nih.gov/pubmed/35335852
http://dx.doi.org/10.3390/pharmaceutics14030474
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