Effect of Corona Block Structure on Telodendrimer Micelles: Probing Exchange Kinetics by Fluorescence Spectroscopy

Telodendrimer micelles with low critical micelle concentrations (CMCs) were synthesized using a hydrophilic poly(sarcosine) (PSar) block and a lysine-based dendritic block carrying four stably conjugated Vadimezan. Variations in the hydrophilic block architecture were made to determine the impact on micelle stability, including variable chain length (n = 50 or 100) and a branched, two-arm structure (n = 50/arm). Despite determining similar CMC (0.8-2.2 μM) values for the micelles, fluorescence resonance energy transfer (FRET) revealed kinetic stability differences. The micelle with the shortest PSar chain showed the fastest unimer exchange kinetics, while longer PSar and branched PSar micelles had similar, overall better stability. Slower unimer re-entry was observed for larger, sterically hindered unimers. The study suggests that hydrophilic block size and topology are equally important in the design criteria as the hydrophobic portion for stability and CMC alone is insufficient to predict micelle behavior in complex biological media.