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Laurenzana A.,Clinical Biomedical science | Fibbi G.,Clinical Biomedical science | Margheri F.,Clinical Biomedical science | Biagioni A.,Clinical Biomedical science | And 3 more authors.
Current Molecular Medicine | Year: 2015

Sprouting angiogenesis consists of the expansion and remodelling of existing vessels, where the vascular sprouts connect each other to form new vascular loops. Endothelial Progenitor Cells (EPCs) are a subtype of stem cells, with high proliferative potential, able to differentiate into mature Endothelial Cells (ECs) during the neovascularization process. In addition to this direct structural role EPCs improve neovascularization, also secreting numerous pro-angiogenic factors able to enhance the proliferation, survival and function of mature ECs, and other surrounding progenitor cells. While sprouting angiogenesis by mature ECs involves resident ECs, the vasculogenic contribution of EPCs is a high hurdle race. Bone marrowmobilized EPCs have to detach from the stem cell niche, intravasate into bone marrow vessels, reach the hypoxic area or tumour site, extravasate and incorporate into the new vessel lumen, thus complementing the resident mature ECs in sprouting angiogenesis. The goal of this review is to highlight the role of the main protease systems able to control each of these steps. The pivotal protease systems here described, involved in vascular patterning in sprouting angiogenesis, are the matrix-metalloproteinases (MMPs), the serineproteinases urokinase-type plasminogen activator (uPA) associated with its receptor (uPAR) and receptorassociated plasminogen/plasmin, the neutrophil elastase and the cathepsins. Since angiogenesis plays a critical role not only in physiological but also in pathological processes, such as in tumours, controlling the contribution of EPCs to the angiogenic process, through the regulation of the protease systems involved, could yield new opportunities for the therapeutic prospect of efficient control of pathological angiogenesis. © 2015 Bentham Science Publishers.

Fedeli S.,University of Florence | Brandi A.,University of Florence | Venturini L.,University of Florence | Chiarugi P.,Clinical Biomedical science | And 7 more authors.
Journal of Materials Chemistry B | Year: 2016

To demonstrate the potential of azido-substituted carbon nanotubes for application in nanomedicine, multiple-decorated oxidized multi-walled carbon nanotubes as drug delivery systems have been synthesized. These DDSs were able to carry doxorubicin inside breast MCF-7 cancer cell lines resulting in an enhanced cytotoxic effect with respect to the free drug. Decoration of the carbon nanotubes was accomplished through both covalent and non-covalent approaches: versatile click reactions and π-π interactions were exploited. To assess the internalization of the carbon nanotubes inside cells, decoration with a BODIPY fluorescent molecule was performed. Furthermore, the nanotubes were decorated with a biotin selector molecule to increase the uptake of the system by cancer cells. Comparative studies were performed on the complete drug delivery system to highlight its effect with respect to the free drug and the contribution of the selector in the internalization efficiency. Finally, preliminary in vivo tests were performed on MCF-7 inoculated mice. A net improvement in efficiency, concerning the minor growth of the tumors, has been found when using doxorubicin loaded on our drug delivery system with respect to free doxorubicin. © 2016 The Royal Society of Chemistry.

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