التفاصيل البيبلوغرافية
العنوان: |
Redox homeostasis disruptors enhanced cuproptosis effect for synergistic photothermal/chemodynamic therapy. |
المؤلفون: |
Liu, Zhen1 (AUTHOR), Ling, Junhong1 (AUTHOR) lingjunhong@zjou.edu.cn, Wang, Nan1 (AUTHOR) nanwang@zjou.edu.cn, Ouyang, Xiao–kun1 (AUTHOR) xkouyang@zjou.edu.cn |
المصدر: |
Journal of Colloid & Interface Science. Jan2025:Part A, Vol. 678, p1060-1074. 15p. |
مصطلحات موضوعية: |
*PHOTOTHERMAL effect, *OXIDATIVE stress, *HYALURONIC acid, *HYDROXYL group, *CELL death |
مستخلص: |
[Display omitted] The combination of chemodynamic therapy (CDT) with photothermal therapy (PTT) is a promising approach to enhance antitumor efficacy of chemotherapeutics. In this paper, we developed novel copper-chelated polydopamine (PDA) nanoparticles (NPs) functionalized with hyaluronic acid (HA) (Cu-PDA-HA NPs) to induce apoptosis and cuproptosis-induced cell death, synergistically combining PTT and CDT. Experimental results revealed that Cu-PDA-HA NPs can respond to excessive glutathione (GSH) and hydrogen peroxide (H 2 O 2) in the tumor microenvironment (TME), which will enable their specific degradation, thereby leading to efficient accumulation of Cu2+ within tumor cells. The released Cu2+ ions were reduced by GSH to generate Cu+, which catalyzed in situ Fenton-like reactions to produce cytotoxic hydroxyl radicals (·OH), disrupting cellular redox homeostasis and promoting apoptosis-related CDT. Meanwhile, the photothermal effect of the Cu-PDA-HA NPs could enhance oxidative stress within the tumor by elevating the temperature and subsequent ·OH production. The enhanced oxidative stress made tumor cells more vulnerable to cuproptosis-induced toxicity. Furthermore, in vivo experiments demonstrated that Cu-PDA-HA NPs can still undergo a temperature increase of 18.9°C following 808 nm near-infrared irradiation (1.0 W/cm2, 5 min). Meanwhile, Cu-PDA-HA NPs were able to induce oligomerization of dihydrolipoamide S-acetyltransferase (DLAT) and down-regulate Fe-S cluster proteins such as ferredoxin (FDX1), thereby activating cuproptosis. Therefore, this study provides a novel approach for designing multifunctional nanoparticles with on-demand Cu2+ release and offers a fresh perspective for exploring synergistic therapeutic strategies involving CDT/PTT/apoptosis/cuproptosis. [ABSTRACT FROM AUTHOR] |
قاعدة البيانات: |
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