Hydrolysable core crosslinked particles for receptor-mediated pH-sensitive anticancer drug delivery

Xifeng Liu, A. Lee Miller, Brian E. Waletzki, Tewodros K. Mamo, Michael J. Yaszemski, Lichun Lu

Research output: Contribution to journalArticle

9 Scopus citations

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 the 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 in an acidic environment due to the ester hydrolysis of PLGA (50 : 50). Furthermore, micelles with folate ligands on the surface showed strong targeting ability and therapeutic efficacy through receptor-mediated endocytosis, as evidenced by efficacious killing of cancer cells and fatal DNA damage. These results imply the promising potential of ligand-conjugated core crosslinked PPF-PLGA-PEG-FA micelles as carrier systems for targeted anti-cancer drug delivery.

Original languageEnglish (US)
Pages (from-to)8840-8847
Number of pages8
JournalNew Journal of Chemistry
Volume39
Issue number11
DOIs
StatePublished - Sep 3 2015

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Materials Chemistry

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