title: Hydrolysable core crosslinked particle for receptor-mediated pH-sensitive anticancer drug delivery.
abstract: Biodegradable micelle systems with both extracellular stabilities and specific targeting properties are highly desirable for anti-cancer drug delivery. Here, we report a biodegradable and crosslinkable poly(propylene fumarate)-co-poly(lactide-co-glycolide)-co-poly(ethylene glycol) (PPF-PLGA-PEG) copolymer conjugated with folate (FA) molecules for receptor-mediated delivery of doxorubicin. Micelles with folate ligands on surface and fumarate bonds within the core were self-assembled and crosslinked, which exhibited better stability against potential physiological conditions during and after drug administration. A pH sensitive drug release profile was observed showing robust release at acidic environment due to the ester hydrolysis of PLGA (50:50). Further, micelles with folate ligands on surface showed strong targeting ability and therapeutic efficacy through receptor-mediated endocytosis, as evidenced by efficacious cancer killing and fatal DNA damage. These results imply promising potential for ligand-conjugated core crosslinked PPF-PLGA-PEG-FA micelles as carrier system for targeted anti-cancer drug delivery.
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: A Lee
authors.initials: AL
authors.lastname: Miller
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Waletzki
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Tewodros K
authors.initials: TK
authors.lastname: Mamo
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Yaszemski
authors.affiliation: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Lichun
authors.initials: L
authors.lastname: Lu