title: Self-Assembled PAEEP-PLLA Micelles with Varied Hydrophilic Block Lengths for Tumor Cell Targeting.
abstract: 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 pathways of PAEEP-PLLA micelles. The shape coupling between micelles and cell membrane facilitated cell surface features such as flattened protrusions (membrane protein) and inward-pointing hollows as well as efficient endocytosis. These results suggested that PAEEP-PLLA self-assembled block copolymer micelles may be an excellent drug delivery system for tumor treatment and that the hydrophilic chain length could regulate drug targeting to tumor cells.
authors.forename: Xuhan
authors.initials: X
authors.lastname: Liu
authors.forename: Xi
authors.initials: X
authors.lastname: Tan
authors.forename: Rong
authors.initials: R
authors.lastname: Rao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University , Beijing 100069, PR China.
authors.forename: Yinghuan
authors.initials: Y
authors.lastname: Li
authors.forename: Xiangliang
authors.initials: X
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D004317:Doxorubicin; D004337:Drug Carriers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D009369:Neoplasms; D011091:Polyesters; D011092:Polyethylene Glycols; D011108:Polymers / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011092:Polyethylene Glycols; C033616:poly(lactide); D004317:Doxorubicin
keywords: PAEEP−PLLA copolymer; hydrophilic chain length; intracellular trafficking; lipid rafts; polymeric micelles; self-assembly