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Updated: Mar 21, 2026

A Facile and Efficient Approach for the Production of Reversible Disulfide Cross-linked Micelles
Published on: December 23, 2016
Hydrolysable core crosslinked particle for receptor-mediated pH-sensitive anticancer drug delivery
Xifeng Liu1, A Lee Miller1, Brian E Waletzki1
1Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
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.
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