期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 36, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2021.102427
关键词
endothelial cells; gold nanoclusters; inflammation; mitochondria; senescence
资金
- Ministry of Science and Technology, Taiwan [MOST 105-2632-B-715-001, MOST 106-2632-B-715-001, MOST 107-2632-B-715-001, MOST 107-2221-E-033-021-MY2]
- MacKay Memorial Hospital [MMH-MM-10859, MMH-MM-10906]
- MacKay Medical College, Taiwan [1081B22, 1081C06, 1091C01]
DHLA-Au NCs, coated with dihydrolipoic acid, interact with mitochondria to attenuate mitochondria-derived reactive oxygen species, providing protection against cellular senescence and inflammation.
Cellular senescence is the progressive impairment of function and proliferation in response to various regulators. Dihydrolipoic acid-coated gold nanoclusters (DHLA-Au NCs), which are molecular clusters with covalently linked dihydroxyl lipoic acid, preserve cellular activities for long-term incubation. DHLA-Au NC delivery was characterized, and we determined the role of growth supplements on internalization, allowing the optimization of DHLA-Au NC bioactivity. In the optimized medium, DHLA-Au NCs attenuated the levels of the senescence-associated phenotype. Molecular mechanism analysis further indicated that during DHLA-Au NC treatment, the activation of the stress signal JNK and its downstream c-Jun were impaired under LPS induction, which led to a decline in AP-1-mediated TNF-alpha transactivation. Confocal microscopy and subcellular fractionation analysis suggested that DHLA-Au NCs interacted with mitochondria through their lipid moiety and attenuated mitochondria-derived reactive oxygen species. With adequate treatment, DHLA-Au NCs show protection against cellular senescence and inflammation in vitro and in vivo. (C) 2021 Elsevier Inc. All rights reserved.
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