Probing the Cellular Delivery Capabilities of Modified Aminoglycosides

Advancement and investigation of cellular delivery vehicles using guanidinoglycosides for the transport of biologically relevant cargos are reported. Insertion of the PEG-modified phospholipid DSPE-PEG-OMe 2000 and a lipophilic guanidinoneomycin derivative on the surface of liposomes diminishes uptake of the nanoassemblies and is dependent on the amount of DSPE-PEG-OMe inserted on the liposome surface. To illustrate this, liposomes with guanidinoneomycin on the bilayer surface (i.e., GNeosomes) were treated with varying amounts of the PEG-modified phospholipid and subsequently analyzed to study the effects on liposomal size, zeta potential, and cellular uptake. By systematically protecting GNeosomes through inserting varying amounts of PEG chains into liposomal bilayers, methodical control over cellular uptake is obtained. Additionally, an analysis of modified amino- and guanidino-glycosides derived from kanamycin, tobramycin, and neomycin in native and mutant CHO cells is examined using confocal microscopy and flow cytometry, illustrating the significance of multivalency for mammalian cell internalization of carriers that specifically interact with cell surface heparan sulfate proteoglycans