Synergistic ROS generation and directional overloading of endogenous calcium induce mitochondrial dysfunction in living cells
Copyright © 2023 Elsevier Ltd. All rights reserved..
Taking advantage of endogenous Ca2+ to upregulate intramitochondrial Ca2+ level has become a powerful mean for mitochondrial dysfunction-mediated tumor therapy. However, the Ca2+ entered into mitochondria is limited ascribing to the uncontrollability and non-selectivity of endogenous Ca2+ transport. It remains a great challenge to make the maximum use of endogenous Ca2+ to ensure sufficient Ca2+ overloading in mitochondria. Herein, we smartly fabricate an intracellular Ca2+ directional transport channel to selectively transport endogenous Ca2+ from endoplasmic reticulum (ER) to mitochondria based on cascade release nanoplatform ABT-199liposomes/doxorubicin@FeIII-tannic acid (ABT@Lip/DOX@Fe-TA). In tumor acidic microenvironment, Fe3+ ions are firstly released and reduced by tannic acid (TA) to Fe2+ for ROS generation. Subsequently, under the NIR light irradiation, the released ABT-199 molecules combine with ROS contribute to the formation of IP3R-Grp75-VDAC1 channel between ER and mitochondria, thus Ca2+ ions are directionally delivered and intramitochondrial Ca2+ level is significantly upregulated. The synergetic ROS generation and mitochondrial Ca2+ overloading effectively intensifies mitochondrial dysfunction, thereby achieving efficient tumor inhibition. This work presents a new insight and promising avenue for endogenous Ca2+-involved tumor therapies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:301 |
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| Enthalten in: |
Biomaterials - 301(2023) vom: 15. Okt., Seite 122284 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Shao, Fengying [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.09.2023 Date Revised 12.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biomaterials.2023.122284 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Taking advantage of endogenous Ca2+ to upregulate intramitochondrial Ca2+ level has become a powerful mean for mitochondrial dysfunction-mediated tumor therapy. However, the Ca2+ entered into mitochondria is limited ascribing to the uncontrollability and non-selectivity of endogenous Ca2+ transport. It remains a great challenge to make the maximum use of endogenous Ca2+ to ensure sufficient Ca2+ overloading in mitochondria. Herein, we smartly fabricate an intracellular Ca2+ directional transport channel to selectively transport endogenous Ca2+ from endoplasmic reticulum (ER) to mitochondria based on cascade release nanoplatform ABT-199liposomes/doxorubicin@FeIII-tannic acid (ABT@Lip/DOX@Fe-TA). In tumor acidic microenvironment, Fe3+ ions are firstly released and reduced by tannic acid (TA) to Fe2+ for ROS generation. Subsequently, under the NIR light irradiation, the released ABT-199 molecules combine with ROS contribute to the formation of IP3R-Grp75-VDAC1 channel between ER and mitochondria, thus Ca2+ ions are directionally delivered and intramitochondrial Ca2+ level is significantly upregulated. The synergetic ROS generation and mitochondrial Ca2+ overloading effectively intensifies mitochondrial dysfunction, thereby achieving efficient tumor inhibition. This work presents a new insight and promising avenue for endogenous Ca2+-involved tumor therapies | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Zhi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Songqin |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yafeng |e verfasserin |4 aut | |
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