Probing Endosomal Escape Using pHlexi Nanoparticles

Nachnicha Kongkatigumjorn, Christina Cortez-Jugo, Ewa Czuba, Adelene S M Wong, Rebecca Y. Hodgetts, Angus P R Johnston, Georgina K. Such

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26 Citations (Scopus)


The effective escape of nanocarriers from endosomal compartments of the cell remains a major hurdle in nanomedicine. The endosomal escape of pH-responsive, self-assembled, dual component particles based on poly[2-(diethylamino)ethyl methacrylate)(PDEAEMA) and poly(ethylene glycol)-b-poly[2-(diethylamino)ethyl methacrylate) (PEG-b-PDEAEMA) has been recently reported. Herein, we report that polymer molecular weight (Mn) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of Mn 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and co-assembled with PEG-b-PDEAEMA (16 kDa) via nanoprecipitation. All particles had similar size, displayed pH-responsive behaviour, and low toxicity regardless of molecular weight. Ovalbumin was loaded in the particles to demonstrate loading and release capabilities and as a marker to study internalization and endosomal escape. Association and endosomal escape was found to depend on molecular weight, with enhanced escape observed for high Mn PDEAEMA: 42% of cells with particle induced endosomal escape for 106 kDa nanoparticles, compared to minimal escape for 7 kDa particles. The results show that a simple variation in molecular weight can enhance the endosomal escape of polymeric carriers, and thus improve their effectiveness for intracellular delivery of therapeutics.

Original languageEnglish
Article number1600248
Number of pages11
JournalMacromolecular Bioscience
Issue number4
Publication statusPublished - 1 Apr 2017


  • Endosomal escape
  • Nanoparticles
  • PH responsive
  • Therapeutic delivery

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