Simultaneously deplete reactive oxygen species and inhibit pyroptosis by dopamine/thioketal-containing polymers delivering disulfiram in combination with Cu(II) for acute glaucoma

Zhou, Xuezhi; Rong, Rong; Liang, Ganghao; Li, Haibo; You, Mengling; Zeng, Zhou; Xiao, Haihua; Ji, Dan; Xia, Xiaobo

doi:10.1016/j.nantod.2022.101668

Cited by 5 publications

(2 citation statements)

References 35 publications

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“… 47 In recent years, novel nanomaterials targeting different mechanisms to counteract against glaucomatous RGC damage have emerged, such as biodegradable polymers utilizing ROS as a trigger to simultaneously activate ROS scavenging and facilitate drug release. 14 , 60 Similar to that approach, our CRCD nanoparticle was able to scavenge ROS, as well as preserving the effects of RAPA to activate autophagy and inhibit inflammation, all of which contributed to the preservation of retinal structure and function.…”

Section: Discussionmentioning

confidence: 95%

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization

Wang,

Dong,

et al. 2024

IJN

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Introduction Glaucoma is a prevalent cause of irreversible vision impairment, characterized by progressive retinal ganglion cells (RGCs) loss, with no currently available effective treatment. Rapamycin (RAPA), an autophagy inducer, has been reported to treat glaucoma in rodent models by promoting RGC survival, but its limited water solubility, systemic toxicity, and pre-treatment requirements hinder its potential clinical applications. Methods Chitosan (CS)-RAPA carbon dot (CRCD) was synthesized via hydrothermal carbonization of CS and RAPA and characterized by transmission electron microscopy, Fourier transform infrared spectra, and proton nuclear magnetic resonance. In vitro assays on human umbilical cord vein endothelial and rat retinal cell line examined its biocompatibility and anti-oxidative capabilities, while lipopolysaccharide-stimulated murine microglia (BV2) assays measured its effects on microglial polarization. In vivo, using a mouse retinal ischemia/reperfusion (I/R) model by acute intraocular pressure elevation, the effects of CRCD on visual function, RGC apoptosis, oxidative stress, and M2 microglial polarization were examined. Results CRCD exhibited good water solubility and anti-oxidative capabilities, in the form of free radical scavenging. In vitro, CRCD was bio-compatible and lowered oxidative stress, which was also found in vivo in the retinal I/R model. Additionally, both in vitro with lipopolysaccharide-stimulated BV2 cells and in vivo with the I/R model, CRCD was able to promote M2 microglial polarization by activating autophagy, which, in turn, down-regulated pro-inflammatory cytokines, such as IL-1β and TNF-α, as well as up-regulated anti-inflammatory cytokines, such as IL-4 and TGF-β. All these anti-oxidative and anti-inflammatory effects ultimately aided in preserving RGCs, and subsequently, improved visual function. Discussion CRCD could serve as a potential novel treatment strategy for glaucoma, via incorporating RAPA into CDs, in turn not only mitigating its toxic side effects but also enhancing its therapeutic efficacy.

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Section: Discussionmentioning

confidence: 95%

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization

Wang,

Dong,

et al. 2024

IJN

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“…During autophagy, the cytosolic form of LC3-I could be converted to the active membrane-bound LC3-II, which indicated autophagosome formation and autophagy initiation by the increased LC3-II/LC3-I ratio. 41 Simultaneously, the formed autophagosome will be internalized and digested by lysosomes and degraded p62 protein (an autophagy substrate). Consequently, the autophagy inhibition could be indicated by the significant increase in the LC3-II/LC3-I ratio and the increased p62 expression, which was further evaluated by the western blotting analysis.…”

Section: Resultsmentioning

confidence: 99%

A dynamic cascade DNA nanocomplex to synergistically disrupt the pyroptosis checkpoint and relieve tumor hypoxia for efficient pyroptosis cancer therapy

Wang,

Ge,

Zhang

et al. 2024

Chem. Sci.

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Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis

Zhao,

Wang,

et al. 2024

Journal of Controlled Release

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Simultaneously deplete reactive oxygen species and inhibit pyroptosis by dopamine/thioketal-containing polymers delivering disulfiram in combination with Cu(II) for acute glaucoma

Cited by 5 publications

References 35 publications

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization

Chitosan-Rapamycin Carbon Dots Alleviate Glaucomatous Retinal Injury by Inducing Autophagy to Promote M2 Microglial Polarization

A dynamic cascade DNA nanocomplex to synergistically disrupt the pyroptosis checkpoint and relieve tumor hypoxia for efficient pyroptosis cancer therapy

Apigenin-7-glucoside-loaded nanoparticle alleviates intestinal ischemia-reperfusion by ATF3/SLC7A11-mediated ferroptosis

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