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Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation

Shaohui Xu Orcid Logo, Pan Zhang, Isabelle Heing-Becker, Junmei Zhang, Peng Tang, Raju Bej Orcid Logo, Sumati Bhatia Orcid Logo, Yinan Zhong, Rainer Haag Orcid Logo

Biomaterials, Volume: 290, Start page: 121844

Swansea University Author: Sumati Bhatia Orcid Logo

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Abstract

Photodynamic therapy (PDT) is emerging as an efficient strategy to combat multidrug-resistant (MDR) cancer. However, the short half-life and limited diffusion of reactive oxygen species (ROS) undermine the therapeutic outcomes of this therapy. To address this issue, a tumor-targeting nanoplatform wa...

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Published in: Biomaterials
ISSN: 0142-9612
Published: Elsevier BV 2022
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URI: https://cronfa.swan.ac.uk/Record/cronfa64855
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spelling v2 64855 2023-11-01 Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation a6b1181ebdbe42bd03b24cbdb559d082 0000-0002-5123-4937 Sumati Bhatia Sumati Bhatia true false 2023-11-01 CHEM Photodynamic therapy (PDT) is emerging as an efficient strategy to combat multidrug-resistant (MDR) cancer. However, the short half-life and limited diffusion of reactive oxygen species (ROS) undermine the therapeutic outcomes of this therapy. To address this issue, a tumor-targeting nanoplatform was developed to precisely deliver mitochondria- and endoplasmic reticulum (ER)-targeting PDT agents to desired sites for dual organelle-targeted PDT. The nanoplatform is constructed by functionalizing molybdenum disulfide (MoS2) nanoflakes with glucose-modified hyperbranched polyglycerol (hPG), and then loading the organelle-targeting PDT agents. The resultant nanoplatform Cy7.5-TG@GPM is demonstrated to mediate both greatly enhanced internalization within MDR cells and precise subcellular localization of PDT agents, facilitating in situ near-infrared (NIR)-triggered ROS generation for augmented PDT and reversal of MDR, causing impressive tumor shrinkage in a HeLa multidrug-resistant tumor mouse model. As revealed by mechanistic studies of the synergistic mitochondria- and ER-targeted PDT, ROS-induced ER stress not only activates the cytosine-cytosine-adenosine-adenosine thymidine/enhancer-binding protein homologous protein (CHOP) pro-apoptotic signaling pathway, but also cooperates with ROS-induced mitochondrial dysfunction to trigger cytochrome C release from the mitochondria and induce subsequent cell death. Furthermore, the mitochondrial dysfunction reduces ATP production and thereby contributes to the reversal of MDR. This nanoplatform, with its NIR-responsive properties and ability to target tumors and subcellular organelles, offers a promising strategy for effective MDR cancer therapy. Journal Article Biomaterials 290 121844 Elsevier BV 0142-9612 Precise subcellular organelle targeting, Endoplasmic reticulum stress, Mitochondrial dysfunction, Molybdenum disulfide, Reversal of tumor multidrug-resistance, Photodynamic therapy 1 11 2022 2022-11-01 10.1016/j.biomaterials.2022.121844 COLLEGE NANME Chemistry COLLEGE CODE CHEM Swansea University The authors acknowledge financial support from the Collaborative Research Center 1449 of the DFG (Germany). S. Xu acknowledges the financial support of the China Scholarship Council (CSC). S. Bhatia acknowledges the financial support from DFG project number 458564133. P. Zhang and Y. Zhong acknowledge the National Natural Science Foundation of China NSFC 52273162 and 51803238. 2024-03-13T16:03:32.6022140 2023-11-01T10:33:31.3440550 Faculty of Science and Engineering School of Engineering and Applied Sciences - Chemistry Shaohui Xu 0000-0001-6470-2755 1 Pan Zhang 2 Isabelle Heing-Becker 3 Junmei Zhang 4 Peng Tang 5 Raju Bej 0000-0002-8453-6966 6 Sumati Bhatia 0000-0002-5123-4937 7 Yinan Zhong 8 Rainer Haag 0000-0003-3840-162x 9
title Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
spellingShingle Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
Sumati Bhatia
title_short Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
title_full Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
title_fullStr Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
title_full_unstemmed Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
title_sort Dual tumor- and subcellular-targeted photodynamic therapy using glucose-functionalized MoS2 nanoflakes for multidrug-resistant tumor ablation
author_id_str_mv a6b1181ebdbe42bd03b24cbdb559d082
author_id_fullname_str_mv a6b1181ebdbe42bd03b24cbdb559d082_***_Sumati Bhatia
author Sumati Bhatia
author2 Shaohui Xu
Pan Zhang
Isabelle Heing-Becker
Junmei Zhang
Peng Tang
Raju Bej
Sumati Bhatia
Yinan Zhong
Rainer Haag
format Journal article
container_title Biomaterials
container_volume 290
container_start_page 121844
publishDate 2022
institution Swansea University
issn 0142-9612
doi_str_mv 10.1016/j.biomaterials.2022.121844
publisher Elsevier BV
college_str Faculty of Science and Engineering
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hierarchy_top_id facultyofscienceandengineering
hierarchy_top_title Faculty of Science and Engineering
hierarchy_parent_id facultyofscienceandengineering
hierarchy_parent_title Faculty of Science and Engineering
department_str School of Engineering and Applied Sciences - Chemistry{{{_:::_}}}Faculty of Science and Engineering{{{_:::_}}}School of Engineering and Applied Sciences - Chemistry
document_store_str 0
active_str 0
description Photodynamic therapy (PDT) is emerging as an efficient strategy to combat multidrug-resistant (MDR) cancer. However, the short half-life and limited diffusion of reactive oxygen species (ROS) undermine the therapeutic outcomes of this therapy. To address this issue, a tumor-targeting nanoplatform was developed to precisely deliver mitochondria- and endoplasmic reticulum (ER)-targeting PDT agents to desired sites for dual organelle-targeted PDT. The nanoplatform is constructed by functionalizing molybdenum disulfide (MoS2) nanoflakes with glucose-modified hyperbranched polyglycerol (hPG), and then loading the organelle-targeting PDT agents. The resultant nanoplatform Cy7.5-TG@GPM is demonstrated to mediate both greatly enhanced internalization within MDR cells and precise subcellular localization of PDT agents, facilitating in situ near-infrared (NIR)-triggered ROS generation for augmented PDT and reversal of MDR, causing impressive tumor shrinkage in a HeLa multidrug-resistant tumor mouse model. As revealed by mechanistic studies of the synergistic mitochondria- and ER-targeted PDT, ROS-induced ER stress not only activates the cytosine-cytosine-adenosine-adenosine thymidine/enhancer-binding protein homologous protein (CHOP) pro-apoptotic signaling pathway, but also cooperates with ROS-induced mitochondrial dysfunction to trigger cytochrome C release from the mitochondria and induce subsequent cell death. Furthermore, the mitochondrial dysfunction reduces ATP production and thereby contributes to the reversal of MDR. This nanoplatform, with its NIR-responsive properties and ability to target tumors and subcellular organelles, offers a promising strategy for effective MDR cancer therapy.
published_date 2022-11-01T16:03:28Z
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