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Rationally designed peptide nanosponges for cell-based cancer therapy.
Nanomedicine : Nanotechnology, Biology, and Medicine 2017 November
A novel type of supramolecular aggregate, named a "nanosponge" was synthesized through the interaction of novel supramolecular building blocks with trigonal geometry. The cholesterol-(K/D)n DEVDGC)3 -trimaleimide unit consists of a trigonal maleimide linker to which homopeptides (either K or D) of variable lengths (n=5, 10, 15, 20) and a consensus sequence for executioner caspases (DEVDGC) are added via Michael addition. Upon mixing in aqueous buffer cholesterol-(K)n DEVDGC)3 -trimaleimides and a 1:1 mixture of cholesterol-(K/D)n DEVDGC)3 -trimaleimides form stable nanosponges, whereas cholesterol-(D)n DEVDGC)3 -trimaleimide is unable to form supramolecular aggregates with itself. The structure of the novel nanosponges was investigated through explicit solvent and then coarse-grained molecular dynamics (MD) simulations. The nanosponges are between 80 nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells.
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