An Ultrasmall Cu/Cu₂O Nanoparticle-Based Diselenide-Bridged Nanoplatform Mediating Reactive Oxygen Species Scavenging and Neuronal Membrane Enhancement for Targeted Therapy of Ischemic Stroke

Abstract

Ischemic stroke is one of the major causes of death and disability worldwide, and an effective and timely treatment of ischemic stroke has been a challenge because of the narrow therapeutic window and the poor affinity with thrombus of the thrombolytic agent. In this study, rPZDCu, a multifunctional nanoparticle (NP) with the effects of thrombolysis, reactive oxygen species (ROS) scavenging, and neuroprotection, was synthesized based on an ultrasmall Cu 4.6 O NP, the thrombolytic agent rt-PA, and docosahexaenoic acid (DHA), which is a major component of the neuronal membrane. rPZDCu showed strong thrombustargeting ability, which was achieved by the platelet cell membrane coating on the NP surface, and a good thrombolytic effect in both the common carotid artery clot model and embolic middle cerebral artery occlusion (MCAO) model of rats. Furthermore, rPZDCu exhibited a good escape from the phagocytosis of macrophages, effective promotion of the polarization of microglia, and efficient recovery of neurobiological and behavioral functions in the embolic MCAO model of rats. This is a heuristic report of (1) the Cu 0 /Cu + NP for the treatments of brain diseases, (2) the integration of DHA and ROS scavengers for central nervous system therapies, and (3) diselenide-based ROS-responsive NPs for ischemic stroke treatments. This study also offers an example of cell membrane-camouflaged stimuli-responsive nanomedicine for braintargeting drug delivery.

A metal–organic cage-derived cascade antioxidant nanozyme to mitigate renal ischemia-reperfusion injury

“…To investigate the biocompatibility of MOC-O in major organs including the heart, liver, lungs and kidneys in mice, tissue samples were collected after two days of treatment and subjected to histological analysis using hematoxylin and eosin (H&E) staining. 2,36 As shown in Fig. 4A, all organs from the three groups exhibited uniform organization with no apparent signs of damage.…”

“…Nonetheless, these bean-shaped organs are quite susceptible to various stressful conditions, particularly I/R injury, due to their high oxygen demand. 1,2 I/R injury is a common cause of kidney damage, often resulting from medical procedures such as kidney transplantation. This injury occurs when the blood supply to the kidneys is temporarily blocked, resulting in a lack of oxygen and nutrients.…”

Simultaneous antioxidant and neuroprotective effects of two-dimensional (2D) MXene-loaded isoquercetin for ischemic stroke treatment

“…Ti 2 C@BSA-ISO has acceptable therapeutic results compared to previous studies. 24,43,60 The long-held belief that titanium is inert and safe for human use can be seen as one of the main reasons for using titanium as an implant. 61 Compared to other elements (Mn, Cu), Ti 2 C@BSA-ISO has a safe composition and has a broader scope for disease treatment.…”

Advanced Nano-Drug Delivery Systems in the Treatment of Ischemic Stroke

“…To sum up, the properties of platelets allow for platelet membrane-coated nanoparticles to be widely used for vascular embolism disease [220][221][222][223][224][225][226]. To sum up, the properties of platelets allow for platelet membrane-coated nanoparticles to be widely used for vascular embolism disease [220][221][222][223][224][225][226].…”