Star-Polymer Unimolecular Micelles for Brain Specific Delivery of Anticancer Drug

Abstract

Abstract Nanocarrier mediated therapeutic delivery to brain tissue remains an impediment by tightly controlled transportation across the blood brain barrier (BBB). Here, we report a well-defined core-shell star-shaped unimolecular micelle (star-UMM) based on biodegradable polycaprolactone platform as an efficient BBB breaching nanovector for brain specific administration of anticancer drug doxorubicin (DOX) and in vivo bioimaging via near-infrared biomarker IR780. The star-UMM was engineered by controlling the polymer topology of hydrophobic and hydrophilic segments from interior to exterior. In vivo imaging in mice was directly evident of prolonged blood circulation of star-UMM for more than 72 h, and the whole-organ image-quantification further substantiated its efficient BBB breaching ability. Star UMM having 15% of DOX exhibited excellent stability in blood circulation, reduction in cardiotoxicity, substantial uptake in the cortical neurons of mouse brain, lysosomal enzymatic-biodegradation, and negligible immunogenicity or necrosis; hence, proving the impact of the star UMM in brain-specific drug delivery.