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ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer

BACKGROUND: Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release...

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Autores principales: Yi, Hanxi, Lu, Wangxing, Liu, Fan, Zhang, Guoqing, Xie, Feifan, Liu, Wenjie, Wang, Lei, Zhou, Wenhu, Cheng, Zeneng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111982/
https://www.ncbi.nlm.nih.gov/pubmed/33975609
http://dx.doi.org/10.1186/s12951-021-00877-6
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author Yi, Hanxi
Lu, Wangxing
Liu, Fan
Zhang, Guoqing
Xie, Feifan
Liu, Wenjie
Wang, Lei
Zhou, Wenhu
Cheng, Zeneng
author_facet Yi, Hanxi
Lu, Wangxing
Liu, Fan
Zhang, Guoqing
Xie, Feifan
Liu, Wenjie
Wang, Lei
Zhou, Wenhu
Cheng, Zeneng
author_sort Yi, Hanxi
collection PubMed
description BACKGROUND: Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy. METHODS: Indocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model. RESULTS: Compared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed. CONCLUSIONS: Lipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00877-6.
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spelling pubmed-81119822021-05-11 ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer Yi, Hanxi Lu, Wangxing Liu, Fan Zhang, Guoqing Xie, Feifan Liu, Wenjie Wang, Lei Zhou, Wenhu Cheng, Zeneng J Nanobiotechnology Research BACKGROUND: Reactive oxygen species (ROS)-responsive drug delivery systems (DDSs) are potential tools to minimize the side effects and substantially enhance the therapeutic efficacy of chemotherapy. However, it is challenging to achieve spatially and temporally controllable and accurate drug release in tumor sites based on ROS-responsive DDSs. To solve this problem, we designed a nanosystem combined photodynamic therapy (PDT) and ROS-responsive chemotherapy. METHODS: Indocyanine green (ICG), an ROS trigger and photosensitizer, and pB-DOX, a ROS-responsive prodrug of doxorubicin (DOX), were coencapsulated in polyethylene glycol modified liposomes (Lipo/pB-DOX/ICG) to construct a combination therapy nanosystem. The safety of nanosystem was assessed on normal HEK-293 cells, and the cellular uptake, intracellular ROS production capacity, target cell toxicity, and combined treatment effect were estimated on human breast cancer cells MDA-MB-231. In vivo biodistribution, biosafety assessment, and combination therapy effects were investigated based on MDA-MB-231 subcutaneous tumor model. RESULTS: Compared with DOX·HCl, Lipo/pB-DOX/ICG showed higher safety on normal cells. The toxicity of target cells of Lipo/pB-DOX/ICG was much higher than that of DOX·HCl, Lipo/pB-DOX, and Lipo/ICG. After endocytosis by MDA-MB-231 cells, Lipo/pB-DOX/ICG produced a large amount of ROS for PDT by laser irradiation, and pB-DOX was converted to DOX by ROS for chemotherapy. The cell inhibition rate of combination therapy reached up to 93.5 %. After the tail vein injection (DOX equivalent of 3.0 mg/kg, ICG of 3.5 mg/kg) in mice bearing MDA-MB-231 tumors, Lipo/pB-DOX/ICG continuously accumulated at the tumor site and reached the peak at 24 h post injection. Under irradiation at this time point, the tumors in Lipo/pB-DOX/ICG group almost disappeared with 94.9 % tumor growth inhibition, while those in the control groups were only partially inhibited. Negligible cardiotoxicity and no treatment-induced side effects were observed. CONCLUSIONS: Lipo/pB-DOX/ICG is a novel tool for on-demand drug release at tumor site and also a promising candidate for controllable and accurate combinatorial tumor therapy. [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-00877-6. BioMed Central 2021-05-11 /pmc/articles/PMC8111982/ /pubmed/33975609 http://dx.doi.org/10.1186/s12951-021-00877-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yi, Hanxi
Lu, Wangxing
Liu, Fan
Zhang, Guoqing
Xie, Feifan
Liu, Wenjie
Wang, Lei
Zhou, Wenhu
Cheng, Zeneng
ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title_full ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title_fullStr ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title_full_unstemmed ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title_short ROS-responsive liposomes with NIR light-triggered doxorubicin release for combinatorial therapy of breast cancer
title_sort ros-responsive liposomes with nir light-triggered doxorubicin release for combinatorial therapy of breast cancer
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111982/
https://www.ncbi.nlm.nih.gov/pubmed/33975609
http://dx.doi.org/10.1186/s12951-021-00877-6
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