A Novel Targeted Nanoparticle for Traumatic Brain Injury Treatment: Combined Effect of ROS Depletion and Calcium Overload Inhibition

Abstract

Survival after severe traumatic brain injury (TBI) depends on minimizing or avoiding secondary insults to the brain. Overproduction of reactive oxygen species (ROS) and Ca2+ influx at the damaged site are the key factors that cause secondary injury upon TBI. Herein, a TBI‐targeted lipid covered radical scavenger nanoparticle is developed to deliver nimodipine (Np) (CL‐PPS/Np), in order to inhibit Ca2+ influx in neurons by Np and to scavenge ROS in the brain trauma microenvironment by poly(propylene sulfide)60 (PPS60) and thus prevent TBI‐associated secondary injury. In post‐TBI models, CL‐PPS/Np effectively accumulates into the wound cavity and prolongs the time of systemic circulation of Np. CL‐PPS/Np can markedly protect the integrity of blood‐brain barrier, prevent brain edema, reduce cell death and inflammatory responses, and promote functional recovery after TBI. These findings may provide a new therapy for TBI to prevent the spread of the secondary injury.

Spatial-temporal changes of iron deposition and iron metabolism after traumatic brain injury in mice

“…Astrocytes are essential for neural redox homeostasis and for protection against nerve injury ( Garg et al, 2011 ). In our study, robust lipid peroxidation was observed in astrocytes after TBI, which may relate to the imbalanced redox in the interstitial microenvironment of the injured cortex ( Qian et al, 2021 ; Han et al, 2022 ). In addition, previous studies have shown that astrocytes do not have a high metabolic requirement for iron ( Cheli et al, 2020 ).…”

Reactive Oxygen Species Scavenging Functional Hydrogel Delivers Procyanidins for the Treatment of Traumatic Brain Injury in Mice

“…Oxidative stress plays an important role in the pathological process of TBI. , The ROS scavenging ability of the GelMA-PPS/PC hydrogel in vitro was verified on the basis of the ROS-dependent products of highly fluoresent 2,7-dichloroflurescein (DCF) produced by alkali-catalyzed or enzymatic hydrolysis of DCFH-DA . After incubation for 1 h, the GelMA-PPS/PC hydrogel immersion solution could inhibit the fluorescence intensity of ROS production induced by 10 mM H 2 O 2 stimulation in HA1800 cells by 80.9%.…”

Recent Advances in Biomaterials‐Based Therapies for Alleviation and Regeneration of Traumatic Brain Injury

“…The decrease of ROS/RNS promotes neuronal survival, alleviates neuroinflammation, and improves outcome of severe TBI. [52] There are three main methods for the adaptive biomaterials to accomplish the property of ROS scavenging, that is, polymers with ROS-responsive units (mainly thioether [53][54][55][56][57] for TBI), biomaterials loaded with bioactive small molecules (e.g., gallic acid (GA), [58] evodiamine, [59,60] procyanidins, [61] and curcumin [53,62] ), and nanozymes that mimic nature enzyme activity (for example, palladium clusters, [63] cerium oxide nanoparticles, [64] and carbon dots (CDs) [65][66][67][68] ). [48] Copyright 2020, Elsevier.…”

“…For example, a multifunctional nano delivery system was fabricated to load the calcium channel blocker nimodipine (Np) to brain trauma area (Figure 3). [56] This nanoparticle is self-assembled through hydrophilic and hydrophobic interactions between lecithin, ROS responsive polymer PPS 60 , 1,2-distearoyl-sn-glycero-3phosphoethanolamine-N-[maleimide(polyethyleneglycol) 2000 ] (DSPE-PEG 2000 ) and DSPE-PEG 2000 modified with cysteinealanine-glutamine-lysine (CAQK) peptide (CAQK-DSPE-PEG 2000 ). CAQK peptide could target to injured brain.…”