Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784676001368768512 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8954063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kimjeongrae sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT choiyongwhan sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT yangsuah sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT leejaewan sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT choijiwoong sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT moonyujeong sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT kimjinseong sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT shimnayeon sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT chohanhee sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT shimmankyu sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT jeonsangmin sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT limdongkwon sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT yoonhongyeol sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses AT kimkwangmeyung sustainedandlongtermreleaseofdoxorubicinfromplgananoparticlesforelicitingantitumorimmuneresponses |