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Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS.

ABSTRACT: The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca²⁺ influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability to achieve effective targeting and to increase the retention time of Mn₃O₄ and nimodipine (MP) in deep injury brain tissue via C-X-C chemokine receptor type 4, integrin beta 1 and macrophage antigen-1. (2) Nimodipine was used to inhibit Ca²⁺ influx, eliminating the ROS at source. (3) Mn₃O₄ further eradicated the existing ROS. In addition, NCM@MP also exhibited desirable properties for T₁ enhanced imaging and low toxicity which may serve as promising multifunctional nanoplatforms for precise therapies. In our study, NCM@MP obviously alleviated oxidative stress response, reduced neuroinflammation, protected blood-brain barrier integrity, relieved brain edema, promoted the regeneration of neurons, and improved the cognition of TBI mice. This study provides a promising TBI management to relieve the secondary spread of damage.

SUBMITTER: Li H

PROVIDER: S-EPMC11320991 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS.

Li Hongqing H Sun Duo D Zhao Zhenghuan Z Fang Jingqin J Li Muyao M Lv Chaoqun C Zhou Weicheng W Li Ning N Guo Yu Y Cao Zhile Z Liu Kaijun K Chen Xiao X

Journal of nanobiotechnology 20240812 1

The secondary injury is more serious after traumatic brain injury (TBI) compared with primary injury. Release of excessive reactive oxygen species (ROS) and Ca<sup>2+</sup> influx at the damaged site trigger the secondary injury. Herein, a neutrophil-like cell membrane-functionalized nanoparticle was developed to prevent ROS-associated secondary injury. NCM@MP was composed of three parts: (1) Differentiated neutrophil-like cell membrane (NCM) was synthesized, with inflammation-responsive ability ...[more]

PMID: 39135044

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Project description:BackgroundThe intestinal epithelial barrier is the first line of defense against pathogens and noxious substances entering the body from the outside world. Through proliferation and differentiation, intestinal stem cells play vital roles in tissue regeneration, repair, and the maintenance of intestinal homeostasis. Inflammatory bowel disease (IBD) is caused by the disruption of intestinal homeostasis through the invasion of toxic compounds and pathogenic microorganisms. Hylotelephium erythrostictum (Miq.) H. Ohba (H. erythrostictum) is a plant with diverse pharmacological properties, including antioxidant, anti-inflammatory, antidiabetic, and antirheumatic properties. However, the roles of H. erythrostictum and its bioactive compounds in the treatment of intestinal injury are unknown.MethodsWe examined the protective effects of H. erythrostictum water extract (HEWE) and H. erythrostictum butanol extract (HEBE) on Drosophila intestinal injury caused by dextran sodium sulfate (DSS) or Erwinia carotovoracarotovora 15 (Ecc15).ResultsOur findings demonstrated that both HEWE and HEBE significantly prolonged the lifespan of flies fed toxic compounds, reduced cell mortality, and maintained intestinal integrity and gut acid‒base homeostasis. Furthermore, both HEWE and HEBE eliminated DSS-induced ROS accumulation, alleviated the increases in antimicrobial peptides(AMPs) and intestinal lipid droplets caused by Ecc15 infection, and prevented excessive ISC proliferation and differentiation by inhibiting the JNK, EGFR, and JAK/STAT pathways. In addition, they reversed the significant changes in the proportions of the gut microbiota induced by DSS. The bioactive compounds contained in H. erythrostictum extracts have sufficient potential for use as natural therapeutic agents for the treatment of IBD in humans.ConclusionOur results suggest that HEWE and HEBE are highly effective in reducing intestinal inflammation and thus have the potential to be viable therapeutic agents for the treatment of gut inflammation.Clinical trial numberNot applicable.

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Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS.

Publications

Neutrophil membrane-derived nanoparticles protect traumatic brain injury via inhibiting calcium overload and scavenging ROS.

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