Moreover, this multifunctional nanoparticle can then be used to confirm that delivery took place using either magnetic resonance imaging (MRI) or fluorescence optical imaging (FOI). Anna Moore, Ph.D., led the research team, which published its results in the journal Nature Medicine.
Delivering siRNA molecules into tumors has proved difficult, although several research teams have found that nanoparticles may be the ideal delivery vehicle for these cancer gene-silencing agents. In this work, Moore and her colleagues used coated iron oxide nanoparticles as the foundation for creating their multifunctional nanoscale drug delivery and imaging device. First, the investigators attached an average of three dye molecules to the iron oxide nanoparticles. Next, they added an average of four membrane-penetrating molecules known as myristoylated polyarginine peptide (MPAP) to the nanoparticle surface. Finally, the researchers linked an average of five siRNA molecules to their multifunctional core.
After injecting this construct into tumor-bearing mice, the investigators were able to track its uptake by the tumors using both MRI, which detects the magnetic iron oxide core, and FOI, which detects the fluorescent molecules attached to the nanoparticle surface. These experiments demonstrated that large numbers of the nanoparticles accumulated in tumors. The investigators were also able to use fluorescence microscopy to show that the siRNA agent was both taken up along with the nanoparticles and able to silence a known cancer gene in the tumors.
This work is detailed in the paper "In vivo imaging of siRNA delivery and silencing in tumors." An abstract of this paper is available through PubMed. View abstract.
nanoncer
Coming at the problem from the perspective of a physicist Dr Nicodemi has found an explanation for the random selection based on thermodynamics. Research has already shown that at the key moment in this process both X chromosomes are brought close together within the cell. The Warwick researcher paper says that what happens next is that material for a "protein plug" then begins to gather around both of the XIST suicide genes on each X Chromosome. This starts a race between the two build ups of protein. Inevitably one of these two nascent protein plugs narrowly wins that race and reaches an energy state in which it can pull together all the material building up in both plugs into a single protein plug. That single plug then closes off one of the XIST suicide genes allowing its host X chromosome to continue to operate. However the other XIST suicide gene is now freed to activate and shuts down its X chromosome.
Since putting forward this explanation researchers in Harvard have observed actual plugs of protein shutting down X chromosome XIST genes in a manner giving further confirmation to Dr Nicodemi's research. So the randomness is explained but what about researchers, other concerns? Dr Nicodemi believes the randomness actually does give an evolutionary advantage. The mechanism means equal numbers of both the maternal and paternal X chromosome are preserved in the gene pool and the resultant population thus has more chance of surviving any biological threat targeted at a single version of the X chromosome.
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