Overcoming Concealment Effects of Targeting Moieties in the PEG Corona: Controlled Permeable Polymersomes Decorated with Folate-Antennae for Selective Targeting of Tumor Cells

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Mohamed A. Yassin - , Leibniz Institute of Polymer Research Dresden, TUD Dresden University of Technology (Author)
  • Dietmar Appelhans - , Leibniz Institute of Polymer Research Dresden (Author)
  • Ralf Wiedemuth - , Department of Neurosurgery, University Hospital Carl Gustav Carus Dresden (Author)
  • Petr Formanek - , Leibniz Institute of Polymer Research Dresden (Author)
  • Susanne Boye - , Leibniz Institute of Polymer Research Dresden (Author)
  • Albena Lederer - , Leibniz Institute of Polymer Research Dresden (Author)
  • Achim Temme - , Department of Neurosurgery, University Hospital Carl Gustav Carus Dresden (Author)
  • Brigitte Voit - , Chair of Organic Chemistry of Polymers, Leibniz Institute of Polymer Research Dresden (Author)

Abstract

In the context of diligent efforts to improve the tumor targeting efficiency of drug carriers, a shape-persistent polymersome which possess a pH-tunable membrane as well as folate targeting antennae is reported. The membrane of such polymersomes behaves as gate which undergoes "on" and "off" switches in response to pH stimuli. Thus, polymersomes can effectively prohibit the premature release of chemotherapeutic agents such as doxorubicin in physiological conditions, but promote drug release once they are triggered in the acidified endosomal compartment. Importantly, the folate moieties are installed on the surface of polymersomes as protruding antennae by doping the polymersomes with folate-terminated block copolymers designed to have longer PEG segments. Thereby, the folate moieties are freed from concealment and steric effects exerted by the dense PEG corona. The cellular uptake of the FA-antennae polymersomes by tumor cells is significantly enhanced facilitated by the freely accessible folate antennae; however, the normal cells record a low level of cellular uptake due to the stealth property of the PEG corona. Overall, the excellent biocompatibility, controlled permeability, targeted internalization, as well as selective cytotoxicity of such polymersomes set up the basis for properly smart carrier for targeted drug delivery.

Details

Original languageEnglish
Pages (from-to)1580-1591
Number of pages12
JournalSmall
Volume11
Issue number13
Publication statusPublished - 2015
Peer-reviewedYes

External IDs

researchoutputwizard legacy.publication#67074
Scopus 84926509776
WOS 000352555000012
PubMed 25363281
ORCID /0000-0002-4531-691X/work/148607584

Keywords

Keywords

  • Copolymer micelles, Block-copolymers, Drug-delivery, In-vitro, Vesicles, Nanoparticles, Doxorubicin, Therapeutics, Nanocarriers, Conjugation