期刊
MACROMOLECULAR BIOSCIENCE
卷 17, 期 4, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/mabi.201600248
关键词
endosomal escape; nanoparticles; pH responsive; therapeutic delivery
资金
- Australian Research Council through the Future Fellowship Scheme [FT120100564, FT110100265]
- Centre of Excellence in Convergent Bio-Nano Science and Technology
- Monash University Larkin's Fellowship Scheme
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 (M-n) can be used to tune endosomal escape of nanoparticle delivery systems. PDEAEMA of M-n 7 kDa, 27 kDa, 56 kDa and 106 kDa was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization and coassembled 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.
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