Whereas the formation and overall stability of hierarchically organized self-assembled supramolecular structures have been extensively investigated, the mechanistic aspects of subcomponent dynamics are often poorly understood or controlled. Here we show that the dynamics of polyamidoamine (PAMAM) dendrimer based micelles can be manipulated by changes in dendrimer generation, pH, and stoichiometry, as proven by NMR and FRET. For this, dendrimers were functionalized with either fluorescein (donor) or rhodamine (acceptor) and encapsulated into separate micelles. Upon mixing, exchange of dendrimers is revealed by an increase in FRET. While dendrimicelles based on dendrimer generations 4 and 5 show a clear increase in FRET in time, revealing the dynamic exchange of dendrimers between micellar cores, generation 6 based micelles appear to be kinetically trapped systems. Interestingly, generation 6 based dendrimicelles prepared at a pH of 7.8 rather than 7.0 do show exchange dynamics, which can be attributed to about 25% less charge of the dendrimer, corresponding to the charge of a virtual generation 5.5 dendrimer at neutral pH. Changing the pH of dendrimicelle solutions prepared at a pH of 7.8 to 7.0 shows the activated release of dendrimers. High-resolution NMR spectra of the micellar core are obtained from a 1.2 GHz spectrometer with sub-micromolar sensitivity, with DOSY discriminating released dendrimers from dendrimers still present in the micellar core. This study shows that dendrimer generation, charge density, and stoichiometry are important mechanistic factors for controlling the dynamics of complex coacervate core micelles. This knowledge can be used to tune micelles between kinetically trapped and dynamic systems, with tuning of exchange and/or release speeds, to be tailored for applications in, e.g., material science, sensors, or drug delivery.
Keywords: Complex Coacervate Core Micelles; Dendrimers; Exchange Dynamics; FRET; NMR; Responsive; Self-Assembly.