Rationally Designed Peptide Nanosponges for Cell-Based Cancer Therapy

Publication date: Available online 25 July 2017 Source:Nanomedicine: Nanotechnology, Biology and Medicine Author(s): Hongwang Wang, Asanka S. Yapa, Nilusha L. Kariyawasam, Tej B. Shrestha, Sebastian O. Wendel, Jing Yu, Marla Pyle, Matthew T. Basel, Aruni P. Malalasekera, Yubisela Toledo, Raquel Ortega, Prem S. Thapa, Hongzhou Huang, Susan X. Sun, Paul E. Smith, Deryl L. Troyer, Stefan H. Bossmann 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)nDEVDGC)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)nDEVDGC)3-trimaleimides and a 1:1 mixture of cholesterol-(K/D)nDEVDGC)3-trimaleimides forms stable nanosponges, whereas cholesterol-(D)nDEVDGC)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 80nm and several micrometers in diameters and virtually non-toxic to monocyte/macrophage-like cells. Graphical abstract
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research