International Journal of Nanomedicine (Dec 2021)

Curcumin Nanoparticles Inhibiting Ferroptosis for the Enhanced Treatment of Intracerebral Hemorrhage

  • Yang C,
  • Han M,
  • Li R,
  • Zhou L,
  • Zhang Y,
  • Duan L,
  • Su S,
  • Li M,
  • Wang Q,
  • Chen T,
  • Mo Y

Journal volume & issue
Vol. Volume 16
pp. 8049 – 8065

Abstract

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Cong Yang,1,* Mengmeng Han,1,2,* Ruoyu Li,1,* Ligui Zhou,1,3 Ying Zhang,1,2 Lining Duan,1,4 Shiyu Su,1,4 Min Li,1,4 Qi Wang,1 Tongkai Chen,1,* Yousheng Mo5,* 1Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 2The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 3Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 4Clinical Medical College of Acupuncture Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, 510405, People’s Republic of China; 5The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tongkai Chen; Yousheng Mo Email [email protected]; [email protected]: Intracerebral hemorrhage (ICH) is a form of severe stroke, the pathology of which is tied closely to a recently discovered form of programmed cell death known as ferroptosis. Curcumin (Cur) is a common phenolic compound extracted from the rhizome of Curcuma longa capable of hematoma volume and associated neurological damage in the context of ICH. Despite exhibiting therapeutic promise, the efficacy of Cur is challenged by its poor water solubility, limited oral bioavailability and inability to efficiently transit across the physiological barriers. Polymer-based nanoparticles (NPs) have widely been employed to aid in drug delivery efforts owing to their ideal biocompatibility and their ability to improve the bioavailability and pharmacokinetics of specific drugs of interest.Methods: In this study, we encapsulated Cur in NPs (Cur-NPs) and explored the effect of these Cur-NPs to enhance Cur delivery both in vitro and in vivo. Furthermore, we evaluated the anti-ferroptosis effect of Cur-NPs in ICH model mice and erastin-treated HT22 murine hippocampal cells.Results: The resultant Cur-NPs were spherical and exhibited a particle size of 127.31± 2.73 nm, a PDI of 0.21± 0.01 and a zeta potential of − 0.25± 0.02 mV. When applied to Madin Darby canine kidney (MDCK) cells in vitro, these Cur-NPs were nonspecifically internalized via multiple endocytic pathways, with plasma membrane microcapsules and clathrin-mediated uptake being the dominant mechanisms. Within cells, these NPs accumulated in lysosomes, endoplasmic reticulum and mitochondria. Cur-NPs were capable of passing through physiological barriers in a zebrafish model system. When administrated to C57BL/6 mice, they significantly improved Cur delivery to the brain. Most notably, when administered to ICH model mice, Cur-NPs achieved superior therapeutic outcomes relative to other treatments. In a final series of experiments, these Cur-NPs were shown to suppress erastin-induced ferroptosis in HT22 murine hippocampal cells.Conclusion: These Cur-NPs represent a promising means of improving Cur delivery to the brain and thereby better treating ICH.Keywords: Intracerebral hemorrhage, nanoparticles, curcumin, brain delivery, blood-brain barrier, ferroptosis

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