Journal
NANO TODAY
Volume 44, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101511
Keywords
Pyroptosis; Oligomycin A; Mitochondrial damage; Oxidative stress; Mild hyperthermia
Categories
Funding
- National Natural Science Foundation of China [21835007, 22005327]
- Key Research Program of Frontier Sciences, Chinese Academy of Sciences, China [ZDBS-LY-SLH029]
- Basic Research Program of Shanghai Municipal Government, China [21JC1406000]
- Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences, China [2021RU012]
- CAMS Innovation Fund for Medical Sciences, China [2021-I2M-5-012]
- China Post-doctoral Science Foundation, China [BX20200345, 2020M671243]
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Programmed cell death (PCD) plays a crucial role in combating tumors in the field of biomedicine. However, malignant tumor cells often develop resistance to commonly used anticancer drugs. A newly designed nanoassembly OA@IR820 targets mitochondria and releases ATP synthase inhibitor OA, leading to ATP synthesis inhibition and mitochondrial dysfunction, thereby promoting oxidative stress-mediated pyroptosis and offering a potential therapeutic strategy for malignant tumor treatment.
Programmed cell death (PCD) plays an important role in triggering the cell death fate against tumor in biomedical frontier. However, malignant tumor cells are often resistant to the commonly used apoptosisinducing anticancer drugs due to the multi-drug resistance of cancer. Considering the mitochondria as the origin of the aerobic respiration and reactive oxygen species, we have designed a biocompatible and mitochondrial-targeting nanoassembly between oligomycin A (OA, an ATP synthase inhibitor) and IR820, which is capable of disassembly in response to NIR laser illumination for OA release, leading to the ATP synthesis inhibition within the electron transport chain, and the mitochondrial de-functioning. Moreover, this process could trigger the electron leak within mitochondria and induce burst releases of reactive oxygen species, thus activating the downstream signaling pathways of pyroptosis, an emerging mitochondria-associated PCD pathway. Such an assembled nanoagonist OA@IR820 could actively induce prominent oxidative stress-mediated pyroptosis for malignant tumor therapy both in vitro and in vivo, presenting a highly potential tumor therapeutics. (c) 2022 Elsevier Ltd. All rights reserved.
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