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Multifunctional magnetic nanocomposites based on mesoporous silica have a wide range of potential applications in catalysis, biomedicine, or sensing. Such particles combine responsiveness to external magnetic fields with other functionalities endowed by the agents loaded inside the pores or conjugated to the particle surface. Different applications might benefit from specific particle morphologies. In the case of biomedical applications, mesoporous silica nanospheres have been extensively studied while nanorods, with a more challenging preparation, have attracted much less attention despite the positive impact on the therapeutic performance shown by seminal studies. Here, we report on a sol-gel synthesis of mesoporous rodlike silica particles of two distinct lengths (1.4 and 0.9 μm) and aspect ratios (4.7 and 2.2) using Pluronic P123 as a structure-directing template and rendering ∼1 g of rods per batch. Iron oxide nanoparticles have been synthesized within the pores yielding maghemite (γ-Fe2O3) nanocrystals of elongated shape (∼7 nm × 5 nm) with a [110] preferential orientation along the rod axis and a superparamagnetic character. The performance of the rods as T2-weighted MRI contrast agents has also been confirmed. In a subsequent step, the mesoporous silica rods were loaded with a cerium compound and their surface was functionalized with fluorophores (fluorescamine and Cyanine5) emitting at λ = 525 and 730 nm, respectively, thus highlighting the possibility of multiple imaging modalities. The biocompatibility of the rods was evaluated in vitro in a zebrafish (Danio rerio) liver cell line (ZFL), with results showing that neither long nor short rods with magnetic particles caused cytotoxicity in ZFL cells for concentrations up to 50 μg/ml. We advocate that such nanocomposites can find applications in medical imaging and therapy, where the influence of shape on performance can be also assessed. ; The authors acknowledge financial support from the Spanish Ministry of Science and Innovation through the RTI2018-096273-B-I00 project, the 'Severo Ochoa' Programme for Centers of Excellence in R&D (CEX2019-000917-S). The Generalitat de Catalunya, project 2017SGR765, is also acknowledged. This research work was performed in the framework of the Nanomedicine CSIC HUB (ref 202180E048).The authors participate in the Aerogels COST ACTION (CA 18125). J.G. received financial support through the "la Caixa" INPhINIT Fellowship Grant for Doctoral Studies at Spanish Research Centers of Excellence (Grant code: LCF/BQ/DI17/11620041), "la Caixa" Banking Foundation (ID100010434), Barcelona, Spain. J.G. was enrolled in the doctoral program in Materials Science at the UAB. M.T. (ref RYC2019-026841-I) has a post-doctoral fellowship "Ramón y Cajal" supported by the "Ministerio de Ciencia e Innovación", Spanish Government. A. G. has been supported by the fellowship from Instituto de Salud Carlos III with FEDER funds (FI17/00073). A.Rosell and A. G. work takes part within the RETICS-INVICTUS PLUS from Instituto de Salud Carlos III with FEDER funds (RD16/0019/0021). G. Antorrena from the LMA at Universidad de Zaragoza is acknowledged for performing XPS measurements. ICTS-CNME at UCM is also acknowledged for offering access to STEM and expertise. The ICMAB Scientific services of electron microscopy, low temperatures and magnetometry, thermal analysis, and X-ray diffraction have performed measurements for the present work. Nico Dix, Joan Esquius, and Xavi Campos are acknowledged by making possible SAXS measurements at the ICMAB X-ray diffraction service. ; Peer reviewed

Altres ajuts: AR is supported by the Miguel Servet programme (CP09/00265) from the Spanish Ministry of Health (Instituto de Salud Carlos III). This work has been funded by Instituto de Salud Carlos III, grant PI10/00694 and the Spanish stroke research network RENEVAS (RD06/0026/0010) co-financed by the European Regional Development Fund (ERDF). This work has been supported also by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreements n° 201024 and n° 202213 (European Stroke Network). ; The identification of circulating endothelial progenitor cells (EPCs) has introduced new possibilities for cell-based treatments for stroke. We tested the angiogenic gene expression of outgrowth endothelial cells (OECs), an EPC subtype capable to shape vessel structures. OECs (at colony or mature stages) from ischemic stroke patients (n=8) were characterized using the RT 2 Profiler TM human angiogenesis PCR Array, and human microvascular endothelial cells (hCMEC/D3) were used as an expression reference of endothelial cells. Colony-OECs showed higher expression of CCL2, ID3, IGF-1, MMP9, TGFBR1, TNFAIP2, TNF and TGFB1. However, BAI-1, NRP2, THBS1, MMP2 and VEGFC expression was increased in mature-OECs (p<0.05). ID3 (p=0.008) and TGFBR1 (p=0.03) genes remained significantly overexpressed in colony-OECs compared to mature-OECs or hCMEC/D3. MMP9 levels were significantly increased in colony-OECs (p=0.025) compared to mature-OECs. Moreover, MMP-2, VEGF-C, THBS1 and NRP-2 gene expression was also significantly increased in mature-OECs compared to hCMEC/D3 (p<0.05). Some of these genes were positively validated by RT-PCR. Our study shows that OECs from stroke patients present higher levels of pro-angiogenic factors at early stages, decreasing in mature OECs when they become more similar to mature microvascular endothelial cells.

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License. ; Hutchinson-Gilford Progeria Syndrome (HGPS) is a premature aging disease in children that leads to early death. Smooth muscle cells (SMCs) are the most affected cells in HGPS individuals, although the reason for such vulnerability remains poorly understood. In this work, we develop a microfluidic chip formed by HGPS-SMCs generated from induced pluripotent stem cells (iPSCs), to study their vulnerability to flow shear stress. HGPS-iPSC SMCs cultured under arterial flow conditions detach from the chip after a few days of culture; this process is mediated by the upregulation of metalloprotease 13 (MMP13). Importantly, double-mutant LmnaG609G/G609GMmp13-/- mice or LmnaG609G/G609GMmp13+/+ mice treated with a MMP inhibitor show lower SMC loss in the aortic arch than controls. MMP13 upregulation appears to be mediated, at least in part, by the upregulation of glycocalyx. Our HGPS-SMCs chip represents a platform for developing treatments for HGPS individuals that may complement previous pre-clinical and clinical treatments. ; This work was funded by FEDER through the Program COMPETE and by Portuguese fund through FCT in context of the projects EXPL/BIM-MED/2267/2013 and POCI-01-0145-FEDER-029229, as well as the European project ERAatUC (ref. 669088).PRP wishes to thank FCT for a BD fellowship (SFRH/BD/71042/2010). AR is supported by the Miguel Servet research contract CPII15/00003 from Instituto de Salud Carlos III, Spain. The FLI is a member of the Leibniz Association and is financiallysupported by the Federal Government of Germany and the State of Thuringia. The authors gratefully acknowledge support from the FLI proteomics core facility. ; info:eu-repo/semantics/publishedVersion