Poly(ethylene glycol) Corona Chain Length Controls End-Group-Dependent Cell Interactions of Dendron Micelles

[Image: see text] To systematically investigate the relationship among surface charge, PEG chain length, and nano–bio interactions of dendron-based micelles (DMs), a series of PEGylated DMs with various end groups (−NH(2), −Ac, and −COOH) and PEG chain lengths (600 and 2000 g/mol) are prepared and tested in vitro. The DMs with longer PEG chains (DM(2K)) do not interact with cells despite their positively charged surfaces. In sharp contrast, the DMs with shorter PEG chains (DM(600)) exhibit charge-dependent cellular interactions, as observed in both in vitro and molecular dynamics (MD) simulation results. Furthermore, all DMs with different charges display enhanced stability for hydrophobic dye encapsulation compared to conventional linear-block copolymer-based micelles, by allowing only a minimal leakage of the dye in vitro. Our results demonstrate the critical roles of the PEG chain length and polymeric architecture on the terminal charge effect and the stability of micelles, which provides an important design cue for polymeric micelles.