A specifically designed nanoconstruct associates, internalizes, traffics in cardiovascular cells, and accumulates in failing myocardium: a new strategy for XXXX diagnostics and therapeutics.

@entity32 @entity712 @entity137 @entity19 @entity4404 @entity2073 @entity6619
AIMS: Ongoing @entity32 and endothelial dysfunction occurs within the local microenvironment of @entity712 , creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous @entity6619 vector ( @entity2073 ), and determine its intravenous accumulation in cardiac tissue in a @entity19 model of @entity712 . METHODS AND RESULTS: In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. @entity137 was investigated by @entity4404 and cell cycle assays. No significant evidence of @entity137 was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo. CONCLUSIONS: Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant @entity137 . Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in @entity712 .
