Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Guo, Xiaoxia, Mei, Jie, Zhang, Chunping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
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
_version_ 1783489560049614848
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
work_keys_str_mv AT guoxiaoxia developmentofdrugdualcarriersdeliverysystemwithmitochondriatargetedandphheatresponsivecapacityforsynergisticphotothermalchemotherapyofovariancancer
AT meijie developmentofdrugdualcarriersdeliverysystemwithmitochondriatargetedandphheatresponsivecapacityforsynergisticphotothermalchemotherapyofovariancancer
AT zhangchunping developmentofdrugdualcarriersdeliverysystemwithmitochondriatargetedandphheatresponsivecapacityforsynergisticphotothermalchemotherapyofovariancancer