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Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer

Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and...

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Autores principales: Zhang, Jibing, Cui, Xiao, Huang, Yujiao, Xu, Xiangdong, Feng, Changshun, Li, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179927/
https://www.ncbi.nlm.nih.gov/pubmed/37175150
http://dx.doi.org/10.3390/molecules28093740
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author Zhang, Jibing
Cui, Xiao
Huang, Yujiao
Xu, Xiangdong
Feng, Changshun
Li, Jun
author_facet Zhang, Jibing
Cui, Xiao
Huang, Yujiao
Xu, Xiangdong
Feng, Changshun
Li, Jun
author_sort Zhang, Jibing
collection PubMed
description Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-β and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8(+) T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm(3), which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy.
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spelling pubmed-101799272023-05-13 Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer Zhang, Jibing Cui, Xiao Huang, Yujiao Xu, Xiangdong Feng, Changshun Li, Jun Molecules Article Breast cancer is one of the most common cancers worldwide, posing a serious threat to human health. Recently, innate immunity has become a widely discussed topic in antitumor research. The STING pathway is an important component of innate immunity, and several STING agonists have been developed and applied in antitumor research. Dimeric amidobenzimidazole (diABZI) is one STING agonist and is a nucleotide analog with low serological stability and cell membrane permeability. In this study, we prepared diABZI-encapsulated liposomes (dLNPs) using the ammonium sulfate gradient method. The average particle size of the dLNPs was 99.76 ± 0.230 nm, and the encapsulation efficiency was 58.29 ± 0.53%. Additionally, in vivo and in vitro assays showed that the dLNPs had a sustained-release effect and that the circulation time in vivo was longer than 48 h. The expression of IFN-β and IFN-γ was elevated in mice treated with dLNPs. Moreover, we found that dLNPs can recruit CD8(+) T cells to tumor tissue and exert antitumor effects. The dLNPs-treated group showed the most significant efficacy: the average tumor volume was 231.46 mm(3), which decreased by 78.16% and 54.47% compared to the PBS group and diABZI group. Meanwhile, the hemolysis rate of the dLNPs was 2%, showing high biocompatibility. In conclusion, dLNPs can effectively suppress tumor growth and possess great potential in breast cancer therapy. MDPI 2023-04-26 /pmc/articles/PMC10179927/ /pubmed/37175150 http://dx.doi.org/10.3390/molecules28093740 Text en © 2023 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
Zhang, Jibing
Cui, Xiao
Huang, Yujiao
Xu, Xiangdong
Feng, Changshun
Li, Jun
Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title_full Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title_fullStr Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title_full_unstemmed Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title_short Anticancer Effect of STING Agonist-Encapsulated Liposomes on Breast Cancer
title_sort anticancer effect of sting agonist-encapsulated liposomes on breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10179927/
https://www.ncbi.nlm.nih.gov/pubmed/37175150
http://dx.doi.org/10.3390/molecules28093740
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