Nanoskopie

Drug delivery systems have attracted considerable attention due to their potential to increase the bioavailability of certain drugs and mitigating side effects by enabling targeted drug release. Reversibly core-crosslinked block copolymer micelles providing a hydrophilic and potentially non-immunogenic shell and a hydrophobic core suitable for the uptake of hydrophobic drugs, are frequently considered, owing their high stability against environmental changes and dilution. Ultimately, triggering core decrosslinking enables implementing strategies for targeted drug release, which requests insights into the impact of varying nanomechanical properties on the stability of individual micelles. Here, Atomic Force Microscopy nanoindentation in aqueous media is applied to intact α-allyl-PEG80-b-P(tBGE52-co-FGE12) micelles to quantify changes in their nanomechanical properties induced by dithio-bismaleimidoethane meditated Diels-Alder crosslinking of furfuryl moieties, and sequential decrosslinking by reduction of its disulfide bond by tris(2-carboxyethyl) phosphine. Changes to the Young’s modulus can be entirely reversed by decrosslinking. Crosslinked and decrosslinked micelles maintain their structural integrity even in diluted aqueous media below the critical micelle concentration in contrast to the initially non-crosslinked micelles. Understanding the structure-property relations associated to the observed augmented mechanical stability in native environments is crucial for improving the efficiency of drug encapsulation, and introducing refined temporal and spatially controlled drug release mechanisms.