Design of nucleic acid-layered double hydroxide nanohybrids

We report here on the design of inorganic–organic hybrid materials, which consist of layered double hydroxides (LDHs) as inorganic carrier and short single-stranded nucleic acids (ssDNA) as organic molecules. LDHs were prepared by the co-precipitation method followed by hydrothermal treatment. A model 12-nucleotide-long sequence was immobilized either by ion exchange or covalent grafting. Both the LDH composition and the nucleic acid-to-particle ratio were opti- mized throughout the synthesis to develop highly stable sus- pensions of the hybrid materials. Structural characterization revealed that the covalent attachment of the ssDNA was suc- cessfully achieved via silanization of the LDHs in aqueous suspension. Covalent linkage of the nucleic acids confers to this model nanoparticulate system promising properties and potential for applications as therapeutic agents. Fragments of nucleic acids could be introduced into living cells without release during the delivery process since LDHs slowly dis- solve in the slightly acidic intracellular space

Angiogenesis in multiple sclerosis and experimental autoimmune encephalomyelitis

Angiogenesis, the formation of new vessels, is found in Multiple Sclerosis (MS) demyelinating lesions following Vascular Endothelial Growth Factor (VEGF) release and the production of several other angiogenic molecules. The increased energy demand of inflammatory cuffs and damaged neural cells explains the strong angiogenic response in plaques and surrounding white matter. An angiogenic response has also been documented in an experimental model of MS, experimental allergic encephalomyelitis (EAE), where blood – brain barrier disruption and vascular remodelling appeared in a pre-symptomatic disease phase. In both MS and EAE, VEGF acts as a pro-inflammatory factor in the early phase but its reduced responsivity in the late phase can disrupt neuroregenerative attempts, since VEGF naturally enhances neuron resistance to injury and regulates neural progenitor proliferation, migration, differentiation and oligodendrocyte precursor cell (OPC) survival and migrati on to demyelinated lesions. An giogenesis, neurogenesis and oligodendroglia maturation are closely intertwined in the neurovascular niches of the subventricular zone, one of the preferential locations of inflammatory lesions in MS, and in all the other temporary vascular niches where the mutual fostering of angiogenesis and OPC maturation occurs. Angiogenesis, induced either by CNS inflammation or by hypoxic stimuli related to neurovascular uncoupling, appears to be ineffective in chronic MS due to a counterbalancing effect of vasoconstrictive mechanisms determined by the reduced axonal activity, astrocyte dysfunction, microglia secretion of free radical species and mitochondrial abnormalities. Thus, angiogenesis, that supplies several trophic factors, should be promoted in therapeutic neuroregeneration efforts to combat the progressive, degenerative phase of MS