Surface Modification of Nanoparticles and Nanovesicles via Click-Chemistry

Surface modification of nanocarriers offers the possibility of targeted drug delivery, which is of major interest in modern pharmaceutical science. Click-chemistry affords an easy and fast way to modify the surface with targeting structures under mild reaction conditions. Here we describe our current method for the post-preparational surface modification of multifunctional sterically stabilized (stealth) liposomes via copper-catalyzed azide-alkyne cycloaddition (CuAAC) and inverse electron demand Diels-Alder norbornene-tetrazine cycloaddition (IEDDA). We emphasize the use of these in a one-pot orthogonal reaction for deep investigation on stability and targeting of nanocarriers. As the production of clickable amphiphilic polymers is a limiting factor in most cases, we also describe our nanocarrier preparation technique called dual centrifugation, which enables the formulation of liposomes on a single-digit milligram scale of total lipid mass.