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Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer
PURPOSE: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers. METHOD...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970626/ https://www.ncbi.nlm.nih.gov/pubmed/32021181 http://dx.doi.org/10.2147/IJN.S226517 |
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author | Guo, Xiaoxia Mei, Jie Zhang, Chunping |
author_facet | Guo, Xiaoxia Mei, Jie Zhang, Chunping |
author_sort | Guo, Xiaoxia |
collection | PubMed |
description | PURPOSE: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers. METHODS: The FRT is a pH-sensitive hollow cage protein with disassembly and reassembly properties and the NGO has a large surface area and a photothermal effect by which it can load and release drugs under near-infrared irradiation (NIR). Due to these unique features, the NGO loaded the anticancer drug resveratrol (RSV) and the conjugated mitochondrion targeted molecule IR780 as IR780-NGO-RSV (INR), the first drug delivery platform. Next, the INR was capsulated by FRT to form the DDDS INR@FRT which was applied for synergistic photothermal-chemotherapy of ovarian cancer. RESULTS: Through a series of characterizations, INR@FRT showed a uniform nanosphere structure and remarkable stability in physiological condition. Heat/pH 5.0 was confirmed to trigger RSV release from the INR@FRT. After taken up by cells, INR@FRT located to the lysosomes where the acidic environment triggered INR release. INR targeted the mitochondrion and released RSV to directly react with organelles, which in turn decreased the mitochondrion membrane potential and caused cell apoptosis. In-vivo experiments showed that INR@FRT combined with NIR irradiation displayed remarkable tumor suppression with a high survival rate after 60 days of treatment. Finally, the biocompatibility of INR@FRT was demonstrated in vitro and in vivo. CONCLUSION: These results highlight the immense potential of INR@FRT as a type of DDDS for the treatment of tumors. |
format | Online Article Text |
id | pubmed-6970626 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-69706262020-02-04 Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer Guo, Xiaoxia Mei, Jie Zhang, Chunping Int J Nanomedicine Original Research PURPOSE: Multifunctional drug delivery systems (DDS) are emerging as a new strategy to highly treat malignant tumors. The aim of this study is to develop a drug dual-carriers delivery system (DDDS) using the natural protein ferritin (FRT) and a nanoscale graphene oxide (NGO) as dual-carriers. METHODS: The FRT is a pH-sensitive hollow cage protein with disassembly and reassembly properties and the NGO has a large surface area and a photothermal effect by which it can load and release drugs under near-infrared irradiation (NIR). Due to these unique features, the NGO loaded the anticancer drug resveratrol (RSV) and the conjugated mitochondrion targeted molecule IR780 as IR780-NGO-RSV (INR), the first drug delivery platform. Next, the INR was capsulated by FRT to form the DDDS INR@FRT which was applied for synergistic photothermal-chemotherapy of ovarian cancer. RESULTS: Through a series of characterizations, INR@FRT showed a uniform nanosphere structure and remarkable stability in physiological condition. Heat/pH 5.0 was confirmed to trigger RSV release from the INR@FRT. After taken up by cells, INR@FRT located to the lysosomes where the acidic environment triggered INR release. INR targeted the mitochondrion and released RSV to directly react with organelles, which in turn decreased the mitochondrion membrane potential and caused cell apoptosis. In-vivo experiments showed that INR@FRT combined with NIR irradiation displayed remarkable tumor suppression with a high survival rate after 60 days of treatment. Finally, the biocompatibility of INR@FRT was demonstrated in vitro and in vivo. CONCLUSION: These results highlight the immense potential of INR@FRT as a type of DDDS for the treatment of tumors. Dove 2020-01-16 /pmc/articles/PMC6970626/ /pubmed/32021181 http://dx.doi.org/10.2147/IJN.S226517 Text en © 2020 Guo et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Guo, Xiaoxia Mei, Jie Zhang, Chunping Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title | Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title_full | Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title_fullStr | Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title_full_unstemmed | Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title_short | Development of Drug Dual-Carriers Delivery System with Mitochondria-Targeted and pH/Heat Responsive Capacity for Synergistic Photothermal-Chemotherapy of Ovarian Cancer |
title_sort | development of drug dual-carriers delivery system with mitochondria-targeted and ph/heat responsive capacity for synergistic photothermal-chemotherapy of ovarian cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6970626/ https://www.ncbi.nlm.nih.gov/pubmed/32021181 http://dx.doi.org/10.2147/IJN.S226517 |
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