Unveiling the effect of stiffness and ligand modification on cellular uptake of micelles

Evaluating the impact of stiffness on the entry cell dynamic parameters of micelles at the single-particle level. • The dynamic parameters of TAT and fluorinated TAT interacting with cell membranes was analyzed at single-molecule level. • Visualizing the morphology and structure changes of cell membranes after interacting with TAT and fluorinated TAT. • The mechanical properties of cell membranes were evaluated after interacting with TAT and fluorinated TAT • The effects of FTAT and TAT on the endocytic pathway of micelles was studied. Taking the advantage of unique amphiphilic structure, nanoscale size, and tunable surface, micelles has been a key platform for targeted nano-drug delivery. To enhance the delivery efficiency, regulating the stiffness and modifying the micelles with ligand is necessary. In this study, the effect of stiffness on the dynamic parameters of micelles entry cell was evaluated at single-particle level, the probability for rigid micelles entry cell is higher, but they need larger force and longer duration. The modification of cationic cell-penetrating peptide TAT and its fluorinated derivative (FTAT) could promote the probability of cellular uptake. The promoting effect was further evaluated by measuring the kinetics of TAT and FTAT interacting with cell membrane at single-molecule level. The FTAT could rapidly bind with cell membrane with higher probability, however, it is also easier to detach from cell membrane. These findings can provide insights into optimizing the micelles for targeted nano-drug delivery. Download: Download high-res image (171KB) Download: Download full-size image