Stimuli-Responsive Nanotherapeutics for Treatment and Diagnosis of Stroke

Abstract

Stroke is the second most common medical emergency and constitutes a significant cause of global morbidity. The conventional stroke treatment strategies, including thrombolysis, antiplatelet therapy, endovascular thrombectomy, neuroprotection, neurogenesis, reducing neuroinflammation, oxidative stress, excitotoxicity, hemostatic treatment, do not provide efficient relief to the patients due to lack of appropriate delivery systems, large doses, systemic toxicity. In this context, guiding the nanoparticles toward the ischemic tissues by making them stimuli-responsive can be a turning point in managing stroke. Hence, in this review, we first outline the basics of stroke, including its pathophysiology, factors affecting its development, current treatment therapies, and their limitations. Further, we have discussed stimuli-responsive nanotherapeutics used for diagnosing and treating stroke with challenges ahead for the safe use of nanotherapeutics.

Pleiotropic Microenvironment Remodeling Micelles for Cerebral Ischemia-Reperfusion Injury Therapy by Inhibiting Neuronal Ferroptosis and Glial Overactivation

“…33 However, achieving prompt drug release at the targeted site is crucial for most nanomedicines to attain therapeutic efficacy. 34,35 Utilizing ROS-sensitive cross-linkers with disulfide or diselenide bonds can ensure responsive drug release at the desired locus. 36 When stimulated by ROS, these cross-linkers can be cleaved, allowing rapid drug release and simultaneous ROS elimination.…”

“…Moreover, incorporating cross-linkers onto the surface of micelles can create a protective barrier that further reduces drug leakage during circulation . However, achieving prompt drug release at the targeted site is crucial for most nanomedicines to attain therapeutic efficacy. , Utilizing ROS-sensitive cross-linkers with disulfide or diselenide bonds can ensure responsive drug release at the desired locus . When stimulated by ROS, these cross-linkers can be cleaved, allowing rapid drug release and simultaneous ROS elimination. , Among these linkers, diselenide bonds are more sensitive to oxidation than disulfide bonds, due to their lower bond energy and lower electronegativity of selenium atoms. , Although diselenide-containing cross-linkers are commonly used in nanodrug delivery systems for tumor treatment, their application in reperfusion injury with high oxidative stress has been rarely reported.…”