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Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES

The starvation therapy mediated by the lonidamine (LND) was limited by the low drug delivery efficiency, off-target effect and compensative glutamine metabolism. Herein, a hyaluronic acid (HA)-modified reduction-responsive micellar nanosystem co-loaded with glycolysis and glutamine metabolism inhibi...

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Autores principales: Fu, Zhenxiang, Du, Huiping, Meng, Siyu, Yao, Mengjiao, Zhao, Pan, Li, Xiang, Zheng, Xinmin, Yuan, Zhang, Yang, Hui, Cai, Kaiyong, Dai, Liangliang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552111/
https://www.ncbi.nlm.nih.gov/pubmed/36238964
http://dx.doi.org/10.1016/j.mtbio.2022.100449
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author Fu, Zhenxiang
Du, Huiping
Meng, Siyu
Yao, Mengjiao
Zhao, Pan
Li, Xiang
Zheng, Xinmin
Yuan, Zhang
Yang, Hui
Cai, Kaiyong
Dai, Liangliang
author_facet Fu, Zhenxiang
Du, Huiping
Meng, Siyu
Yao, Mengjiao
Zhao, Pan
Li, Xiang
Zheng, Xinmin
Yuan, Zhang
Yang, Hui
Cai, Kaiyong
Dai, Liangliang
author_sort Fu, Zhenxiang
collection PubMed
description The starvation therapy mediated by the lonidamine (LND) was limited by the low drug delivery efficiency, off-target effect and compensative glutamine metabolism. Herein, a hyaluronic acid (HA)-modified reduction-responsive micellar nanosystem co-loaded with glycolysis and glutamine metabolism inhibitor (LND and bis-2-(5-phenylacetmido-1,2,4-thiadiazol-2-yl)ethyl sulfide, BPTES) was constructed for tumor-targeted dual-starvation therapy. The in vitro and in vivo results collectively suggested that the fabricated nanosystem could effectively endocytosed by tumor cells via HA receptor-ligand recognition, and rapidly release starvation-inducers LND and BPTES in response to the GSH-rich intratumoral cytoplasm. Furthermore, the released LND and BPTES were capable of inducing glycolysis and glutamine metabolism suppression, and accompanied by significant mitochondrial damage, cell cycle arrest and tumor cells apoptosis, eventually devoting to the blockade of the energy and substance supply and tumor killing with high efficiency. In summary, HPPPH@L@B nanosystem significantly inhibited the compensatory glycolysis and glutamine metabolism via the dual-starvation therapy strategy, blocked the indispensable energy and substance supply of tumors, consequently leading to the desired tumor starvation and effective tumor killing with reliable biosafety.
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spelling pubmed-95521112022-10-12 Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES Fu, Zhenxiang Du, Huiping Meng, Siyu Yao, Mengjiao Zhao, Pan Li, Xiang Zheng, Xinmin Yuan, Zhang Yang, Hui Cai, Kaiyong Dai, Liangliang Mater Today Bio Full Length Article The starvation therapy mediated by the lonidamine (LND) was limited by the low drug delivery efficiency, off-target effect and compensative glutamine metabolism. Herein, a hyaluronic acid (HA)-modified reduction-responsive micellar nanosystem co-loaded with glycolysis and glutamine metabolism inhibitor (LND and bis-2-(5-phenylacetmido-1,2,4-thiadiazol-2-yl)ethyl sulfide, BPTES) was constructed for tumor-targeted dual-starvation therapy. The in vitro and in vivo results collectively suggested that the fabricated nanosystem could effectively endocytosed by tumor cells via HA receptor-ligand recognition, and rapidly release starvation-inducers LND and BPTES in response to the GSH-rich intratumoral cytoplasm. Furthermore, the released LND and BPTES were capable of inducing glycolysis and glutamine metabolism suppression, and accompanied by significant mitochondrial damage, cell cycle arrest and tumor cells apoptosis, eventually devoting to the blockade of the energy and substance supply and tumor killing with high efficiency. In summary, HPPPH@L@B nanosystem significantly inhibited the compensatory glycolysis and glutamine metabolism via the dual-starvation therapy strategy, blocked the indispensable energy and substance supply of tumors, consequently leading to the desired tumor starvation and effective tumor killing with reliable biosafety. Elsevier 2022-10-03 /pmc/articles/PMC9552111/ /pubmed/36238964 http://dx.doi.org/10.1016/j.mtbio.2022.100449 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Full Length Article
Fu, Zhenxiang
Du, Huiping
Meng, Siyu
Yao, Mengjiao
Zhao, Pan
Li, Xiang
Zheng, Xinmin
Yuan, Zhang
Yang, Hui
Cai, Kaiyong
Dai, Liangliang
Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title_full Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title_fullStr Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title_full_unstemmed Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title_short Tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded LND and BPTES
title_sort tumor-targeted dual-starvation therapy based on redox-responsive micelle nanosystem with co-loaded lnd and bptes
topic Full Length Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9552111/
https://www.ncbi.nlm.nih.gov/pubmed/36238964
http://dx.doi.org/10.1016/j.mtbio.2022.100449
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