Hierarchically built-up multicompartment nanoaggregate systems are of interest for, e.g., novel materials and medicine. Here we present a versatile strategy to generate and unambiguously... Show moreHierarchically built-up multicompartment nanoaggregate systems are of interest for, e.g., novel materials and medicine. Here we present a versatile strategy to generate and unambiguously characterize complex coacervate-core micelles by exploiting four different dendrimeric subcomponents as core-units. The resulting mesoscale structures have a hydrodynamic diameter of 50 nm and a core size of 33 nm, and host about thirty 6th generation polyamidoamine (PAMAM) dendrimers. We have used FRET (efficiency of similar to 0.2) between fluorescein and rhodamine moieties immobilized on separate PAMAM dendrimers (G6-F and G6-R, respectively) to prove synchronous encapsulation in the micelle core. Tuning the proximity of the FRET pair molecules either by varying the G6-F : G6-R ratio, or by co-assembling non-functionalized dendrimer (G6-E) in the core, reveals the optimal FRET efficiency to occur at a minimum of 70% loading with G6-F and G6-R. Additional co-encapsulation of 6th generation gold dendrimer-encapsulated nanoparticles (G6-Au) in the micelle core shows a dramatic reduction of the FRET efficiency, which can be restored by chemical etching of the gold nanoparticles from within the micellar core with thiols, leaving the micelle itself intact. This study reveals the controlled co-assembly of up to four different types of subcomponents in one single micellar core and concomitantly shows the wide variety of structures that can be made with a well-defined basic set of subcomponents. It is straightforward to design related strategies, to incorporate inside one micellar core, e.g., even more than 4 different dendrimers, or other classes of (macro)molecules, with different functional groups, other FRET pairs or different encapsulated metal nanoparticles. Show less
The use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application... Show moreThe use of mammalian cells for therapeutic applications is finding its way into modern medicine. However, modification or “training” of cells to make them suitable for a specific application remains complex. By envisioning a chemical toolbox that enables specific, but straight-forward and generic cellular functionalization, we investigated how membrane-receptor (pre)targeting could be combined with supramolecular host-guest interactions based on β-cyclodextrin (CD) and adamantane (Ad). The feasibility of this approach was studied in cells with membranous overexpression of the chemokine receptor 4 (CXCR4). By combining specific targeting of CXCR4, using an adamantane (Ad)-functionalized Ac-TZ14011 peptide (guest; KD = 56 nM), with multivalent host molecules that entailed fluorescent β-CD-Poly(isobutylene-alt-maleic-anhydride)-polymers with different fluorescent colors and number of functionalities, host-guest cell-surface modifications could be studied in detail. A second set of Ad-functionalized entities enabled introduction of additional surface functionalities. In addition, the attraction between CD and Ad could be used to drive cell-cell interactions. Combined we have shown that supramolecular interactions, that are based on specific targeting of an overexpressed membrane- receptor, allow specific and stable, yet reversible, surface functionalization of viable cells and how this approach can be used to influence the interaction between cells and their surroundings. Show less
