Targeted Drug Delivery to Stroke via Chemotactic Recruitment of Nanoparticles Coated with Membrane of Engineered Neural Stem Cells

Here a membrane ‐coating approach to display large transmembrane protein receptors to the surface of nanoparticles for drug delivery to the brain is developed and validated. The study also establishes a new formulation of glyburide that can be translated into clinical applications to improve clinical management of brain injuries. AbstractCell membrane coating has recently emerged as a promising biomimetic approach to engineering nanoparticles (NPs) for targeted drug delivery. However, simple cell membrane coating may not meet the need for efficient drug delivery to the brain. Here, a novel molecular engineering strategy to modify the surface of NPs with a cell membrane coating for enhanced brain penetration is reported. By using poly(lactic ‐co‐glycolic) acid NPs as a model, it is shown that delivery of NPs to the ischemic brain is enhanced through surface coating with the membrane of neural stem cells (NSCs), and the delivery efficiency can be further increased using membrane isolated from NSCs engineered for overexpression of CXCR4. I t is found that this enhancement is mediated by the chemotactic interaction of CXCR4 with SDF‐1, which is enriched in the ischemic microenvironment. It is demonstrated that the resulting CXCR4‐overexpressing membrane‐coated NPs, termed CMNPs, significantly augment the efficacy of glyburide, an anti‐edema agent, for stroke treatment. The study suggests a new approach to improving drug delivery to the ischemic brain and establishes...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research