title: Probing Endosomal Escape Using pHlexi Nanoparticles.
abstract: 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 Mn7 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 MnPDEAEMA: 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.
authors: School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Nachnicha
authors: N
authors: Kongkatigumjorn
authors: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.
authors: Christina
authors: C
authors: Cortez-Jugo
authors: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.
authors: Ewa
authors: E
authors: Czuba
authors: School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia.|ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.
authors: Adelene S M
authors: AS
authors: Wong
authors: School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Rebecca Y
authors: RY
authors: Hodgetts
authors: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, 3052, Australia.
authors: Angus P R
authors: AP
authors: Johnston
authors: School of Chemistry, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors: Georgina K
authors: GK
authors: Such
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002452:Cell Count; D002470:Cell Survival; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry; D051379:Mice; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry; D010047:Ovalbumin / Q000378:metabolism; D010316:Particle Size
chemical_list: D005452:Fluoresceins; D008689:Methacrylates; D009757:Nylons; C109846:poly(2-(diethylamino)ethyl methacrylate); D010047:Ovalbumin; C007740:fluorexon
keywords: endosomal escape; nanoparticles; pH responsive; therapeutic delivery