Preferential Targeting Cerebral Ischemic Lesions with Cancer Cell-Inspired Nanovehicle for Ischemic Stroke Treatment

Abstract

The poor drug delivery to cerebral ischemic regions is a key challenge of ischemic stroke treatment. Inspired by the intriguing blood−brain barrier (BBB)-penetrating ability of 4T1 cancer cells upon their brain metastasis, we herein designed a promising biomimetic nanoplatform by camouflaging a succinobucol-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB), aiming to promote the preferential targeting of cerebral ischemic lesions to attenuate the ischemia/ reperfusion injury. In transient middle cerebral artery occlusion (tMCAO) rat models, MPP/SCB could be preferentially delivered to the ischemic hemisphere with a 4.79-fold higher than that in the normal hemisphere. Moreover, MPP/SCB produced notable enhancement of microvascular reperfusion in the ischemic hemisphere, resulting in a 69.9% reduction of infarct volume and showing remarkable neuroprotective effects of tMCAO rats, which was superior to the counterpart uncamouflaged nanovehicles (PP/SCB). Therefore, this design provides a promising nanoplatform to target the cerebral ischemic lesions for ischemic stroke therapy.

pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke

“…Studies demonstrated that changes in tissue water content altered the histomorphology and the ratio of free water to bound water, and different transverse relaxation times T2 could be measured, while signal intensity and T2 values reflect the degree of brain edema. − Our results showed an increase in T2 values after cerebral ischemia; RAPA@NPs treatment markedly reduced the T2 values in the ischemic hemisphere compared to the PBS and RAPA treatments (Figure A,B). T2 mapping is sensitive to water content and is commonly used for the noninvasive assessment of the edematous response after cerebral and myocardial ischemia-reperfusion. − However, T2 values may also be affected by other factors, such as oxygenation and deoxygenation status, tissue microperfusion, and hemorrhage, which need to be studied in detail. To obtain more accurate results, the wet and dry weight of post-mortem brain tissue after 24 h of reperfusion in each group was determined to further assess the brain tissue water content, which is the gold standard technique for measuring cerebral edema.…”

Construction of Nanocarriers Based on Endogenous Cell Membrane and Their Application in Nanomedicine

“…EMBNs is synthesized by encapsulating pH‐sensitive succinic anhydride polymer nanoparticles (MPP/SCB) in a CCMs, so as to improve targeting and therapeutic effect of cerebral ischemia injury (Figure 5A). [ 91 ] In addition, in the drug delivery of antibiotics, the targeted drug delivery ability of antibiotics can also significantly reduce the drug dose, so as to achieve the purpose of improving the bioavailability of antibiotics. [ 72 ] The results showed that CCMs‐coated NPs significantly improved targeted cell uptake due to homologous targeting compared with simple NPs and other membrane‐encase NPs.…”

“…(A) The preparation of MPP/SCB and the mechanism of its therapeutic effect. [ 91 ] Reproduced with permission from Ref. [91].…”

Progresses and Prospects of Neuroprotective Agents-Loaded Nanoparticles and Biomimetic Material in Ischemic Stroke

“…Common antioxidant drugs contain Tempol ( Hosoo et al, 2017 ), edaravone (EDV) ( Jin et al, 2017 ), succinobucol ( He et al, 2021b ), and curcumin ( Wang et al, 2019 ), which were extracted naturally from plants or artificially synthesized. NPs as a feasible strategy extend the half-life of these drugs and improve their ability to cross the BBB, so improve the therapeutic effect of these drugs of ischemic stroke.…”

“…SCB has the capacity of preventing the mitochondrial dysfunction induced by tert-butyl hydroperoxide, which provides lines of evidence to clarify SCB as a potential neuroprotective agent ( Colle et al, 2013 ). A SCB-loaded pH-sensitive polymeric nanovehicle with a 4T1 cell membrane (MPP/SCB) ( He et al, 2021b ), improves the ability to penetrate the BBB and increases the targeting effect of cerebral ischemic lesions. The fluorescence signals of ROS in PC12 cells treated with MPP/SCB was significantly weaker.…”