Platelet Membrane Biomimetic Magnetic Nanocarriers for Targeted Delivery and in Situ Generation of Nitric Oxide in Early Ischemic Stroke

Abstract

Early diagnosis and treatment of acute ischemic stroke poses a significant challenge due to its suddenness and short therapeutic time window. Human endogenous cells derived biomimetic drug carriers have provided new options for stroke theranostics since these cells have higher biosafety and targeting abilities than artificial carriers. Inspired by natural platelets (PLTs) and their role in targeting adhesion to the damaged blood vessel during thrombus formation, we fabricated a biomimetic nanocarrier comprising a PLT membrane envelope loaded with L-arginine and γ-Fe 2 O 3 magnetic nanoparticles (PAMNs) for thrombus-targeted delivery of L-arginine and in situ generation of nitric oxide (NO). Results demonstrate that the engineered 200 nm PAMNs inherit the natural properties of the PLT membrane and achieve rapid targeting to ischemic stroke lesions under the guidance of an external magnetic field. Subsequent to the release of Larginine at the thrombus site, endothelial cells produce NO, which promotes vasodilation to disrupt the local PLT aggregation. Rapid targeting of PAMNs to stroke lesions as well as in situ generation of NO prompts vasodilation, recovery of blood flow, and reperfusion of the stroke microvascular. Thus, these PLT membrane derived nanocarriers are diagnostically beneficial for localizing stroke lesions and a promising modality for executing therapies.

Drug Targeting via Platelet Membrane–Coated Nanoparticles

“…Meanwhile, PDT uses the photosensitizers to generate singlet oxygen upon laser excitation to kill cancer cells. Both therapies are considered minimum [29] Rapamycin (used as an immunosuppressant) [31] Inserted with lipid-chelated gadolinium (an MRI contrast agent) in the membrane [27] Angioplasty-induced restenosis PLGA nanoparticles Docetaxel (a cytotoxic drug) [33] Poly(amidoamine)-polyvalerolactone nanoclusters JQ1 (an endothelium-protective epigenetic inhibitor) [34] Myocardial ischemia and reperfusion injuries PLGA nanoparticles Secretome of cardiac stem cells (promote cardiac repair and regeneration) [36] Ischemic stroke Sulfur hexafluoride gas Sulfur hexafluoride gas [38] Dextran nanoparticles ZL006e (a neuroprotectant) and rtPA (a thrombolytic drug) [39] Iron oxide (γ-Fe 2 O 3 ) nanoparticles L-arginine (a precursor for biosynthesis of nitric oxide gas) [40] Pulmonary embolism Gold nanorods Urokinase plasminogen activator (a thrombolytic drug) [47] PLGA nanoparticles rtPA [44] invasive for cancer treatment. Recently, verteporfin, a photodynamic agent, was encapsulated into PLGA nanoparticles and coated with platelet membrane (denoted as "NP-Ver@P") for cancer PDT.…”

Nanomedicine for Ischemic Stroke

“…Furthermore, the release of L-arginine at ischemic lesions promoted vasodilation and the thrombosis was disrupted to restore the blood flow. This study showed that PAMNs may be a useful tool for both MRI imaging and targeted therapy for ischemic stroke [ 61 ].…”

The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation

“…In a recent study, platelet membrane vesicles (PMVs) were exploited as a specific thrombus-targeting strategy for the treatment of ischemic stroke. PMVs, which have inherited targeting ligands to thrombus and nearby endothelial cells, can specifically bind to the thrombus [ 249 ]. These PMVs loaded with natural compound and magnetic NPs can reach the stroke-induced damaged sites faster and more active when external magnetic fields are applied near the damaged sites, because of the magnetic guidance effect.…”

“…These PMVs loaded with natural compound and magnetic NPs can reach the stroke-induced damaged sites faster and more active when external magnetic fields are applied near the damaged sites, because of the magnetic guidance effect. Thus, biomimetic exosomes can be promising nanocarriers exhibiting specific neuroinflammation-targeting delivery with the application of external magnetic field or HIFU or extra surface functionalization [ 249 , 250 ].…”