ALBERT

Description: Developing multifunctional and biocompatible drug delivery nanoplatforms that integrate high drug loads and multiple imaging modalities avoiding cross-interferences is extremely challenging. Here we report on the successful chemical reaction of the high quantum yield biodegradable and photoluminescent polyester (BPLP) with the poly(lactic-co-glycolic acid) (PLGA) polymer to fabricate biocompatible photoluminescent nanocapsules (NCs). Furthermore, we transform the PLGA-BPLP NCs into a magnetic resonance (MR)/photoluminescence dual-modal imaging theranostic platform by incorporating superparamagnetic iron oxide nanoparticles (SPIONs) into the polymeric shell. In vitro phantoms confirmed the excellent MRI-r2 relaxivity values of the NCs whilst the cellular uptake of these NCs was clearly observed by fluorescence optical imaging. Besides, the NCs (mean size ~270 nm) were loaded with ~1 wt% of a model protein (BSA) and their PEGylation provided a more hydrophilic surface. The NCs show biocompatibility in vitro, as hCMEC/D3 endothelial cells viability was not affected for particle concentration up to 500 μg/mL. Interestingly, NCs decorated with SPIONs can be exploited for magnetic guiding and retention.

Description: Background Cell-based therapeutic strategies have been proposed as an alternative for brain repair after stroke, but their clinical application has been hampered by potential adverse effects in the long term. The present study was designed to test the effect of the secretome of endothelial progenitor cells (EPCs) from stroke patients (scCM) on in vitro human models of angiogenesis and vascular barrier. Methods Two different scCM batches were analysed by mass spectrometry and a proteome profiler. Human primary CD34+-derived endothelial cells (CD34+-ECs) were used for designing angiogenesis studies (proliferation, migration, and tubulogenesis) or in vitro models of EC monolayer (confluent monolayer ECs—CMECs) and blood–brain barrier (BBB; brain-like ECs—BLECs). Cells were treated with scCM (5 μg/mL) or protein-free endothelial basal medium (scEBM—control). CMECs or BLECs were exposed (6 h) to oxygen–glucose deprivation (OGD) conditions (1% oxygen and glucose-free medium) or normoxia (control—5% oxygen, 1 g/L of glucose) and treated with scCM or scEBM during reoxygenation (24 h). Results The analysis of different scCM batches showed a good reproducibility in terms of protein yield and composition. scCM increased CD34+-EC proliferation, tubulogenesis, and migration compared to the control (scEBM). The proteomic analysis of scCM revealed the presence of growth factors and molecules modulating cell metabolism and inflammatory pathways. Further, scCM decreased the permeability of CMECs and upregulated the expression of the junctional proteins such as occludin, VE-cadherin, and ZO-1. Such effects were possibly mediated through the activation of the interferon pathway and a moderate downregulation of Wnt signalling. Furthermore, OGD increased the permeability of both CMECs and BLECs, while scCM prevented the OGD-induced vascular leakage in both models. These effects were possibly mediated through the upregulation of junctional proteins and the regulation of MAPK/VEGFR2 activity. Conclusion Our results suggest that scCM promotes angiogenesis and the maturation of newly formed vessels while restoring the BBB function in ischemic conditions. In conclusion, our results highlight the possibility of using EPC-secretome as a therapeutic alternative to promote brain angiogenesis and protect from ischemia-induced vascular leakage.