Engineered Biomimetic Nanoplatform Protects the Myocardium Against Ischemia/Reperfusion Injury by Inhibiting Pyroptosis

Abstract

Protection of cardiomyocytes against oxidative stress is vital to alleviate myocardial ischemia/reperfusion injury (MI/RI). However, antioxidative treatment is hampered by the lack of safe and effective therapeutics. Polydopamine (PDA), as a biodegradable class of nanomaterial with excellent antioxidant properties, has shown great potential in treating MI/RI. To achieve site-specific antioxidative efficacy, we established a PDA-based biomimetic nanoplatform (PDA@M), which consisted of a polydopamine core and a macrophage membrane shell to form a shell–core structure. By inheriting the inherent migration capability of macrophages, PDA@M was able to target the infarcted myocardium and exert an antioxidative effect to protect the myocardium. The results demonstrated that the accumulation of the membrane-wrapped nanoparticles (NPs) in the infarcted myocardium was greatly increased as compared with PDA alone, which effectively relieved the MI/RI-induced oxidative stress. PDA@M largely decreased the infarct size and improved the cardiac function post-MI/RI. Our study revealed that PDA@M could inhibit cell pyroptosis by suppressing the NLRP3/caspase-1 pathway, which is known to play a significant role in the antioxidant signaling pathway. In summary, PDA@M can target the infarcted myocardium and exert antioxidative and antipyroptosis functions to protect the myocardium against MI/RI-induced oxidative stress, suggesting that it may prove to be a potential therapeutic agent for MI/RI.

Prussian Blue Nanozyme as a Pyroptosis Inhibitor Alleviates Neurodegeneration

“…[17] Therefore, effectively eliminating excess mitochondrial ROS may be a potential strategy to block NLRP3-mediated pyroptosis for the alleviation of PD. [17,19] Artificial nanozymes have attracted extensive interest in the past decade owing to their prominent advantages, including adjustable catalytic activities, multiple enzyme-like activities, and high stability. [20,21] To date, more than 900 types of nanozymes from different materials have been reported.…”

“…[ 17 ] Therefore, effectively eliminating excess mitochondrial ROS may be a potential strategy to block NLRP3‐mediated pyroptosis for the alleviation of PD. [ 17,19 ]…”

Targeting Ferroptosis by Polydopamine Nanoparticles Protects Heart against Ischemia/Reperfusion Injury

“…Dopamine is one of the inotropic agents applied clinically to improve cardiac functions in patients suffering from cardiac insufficiency . Studies have reported that dopamine could be assembled into polydopamine, which has been widely used in biomedical fields due to its favorable biocompatibility and biodegradability. − Interestingly, due to the presence of phenolic hydroxyl groups, polydopamine exhibits excellent chelating efficiencies against metal ions, including copper, iron, and manganese. , In addition, polydopamine has been identified as an antioxidant that can inhibit inflammation and oxidative stress. , Given the metal ion-chelating, anti-inflammation, and antioxidative stress effects of polydopamine, polydopamine is naturally considered to be an appropriate drug candidate for alleviating myocardial I/R injury and improving cardiac function.…”

Pyroptosis in inflammatory diseases and cancer

“…Wei et al reported that a polydopamine-based biomimetic nanoplatform (PDA@M) can inhibit pyroptosis to protect the myocardium against IRI. PDA@M consists of a polydopamine core and a macrophage membrane shell, to achieve site-specific antioxidative efficacy 68 . The results demonstrated that PDA@M targets the infarcted myocardium to suppress the NLRP3/caspase-1 pathway, thus exerting antioxidative and antipyroptosis functions, suggesting that it may serve as a potential therapeutic agent for IRI.…”