Self-Assembled PAEEP-PLLA Micelles with Varied Hydrophilic Block Lengths for Tumor Cell Targeting.

The properties of hydrophilic shell in micelles significantly affect the interaction between micelles and cells. Compared with frequently used polyethylene glycol (PEG) as the hydrophilic block, polyphosphoesters (PPEs) are superior in functionality, biocompatibility, and degradability. A series of amphiphilic poly(aminoethyl ethylene phosphate)/poly(l-lactide acid) (PAEEP–PLLA) copolymers were synthesized with hydrophilic PAEEP with different chain lengths. The corresponding self-assembled micelles were used for doxorubicin (Dox) entrapment. The length of hydrophilic PAEEP block on the shell affected the structure of micelles. PAEEPm–PLLA168 (m = 130 or 37) polymers formed vesicles, while PAEEPm–PLLA168 (m = 15 or 9) formed large compound micelles (LCMs), suggesting a difference in tumor cell uptake and intracellular trafficking. PAEEP15–PLLA168 polymer showed superiority on cellular uptake amount, intracellular drug release, and cell apoptosis. Lipid rafts and macropinocytosis are the leading endocytic ...