Journal article

Super-resolution Imaging of Proton Sponge-Triggered Rupture of Endosomes and Cytosolic Release of Small Interfering RNA

Marcin Wojnilowicz, Agata Glab, Alessandro Bertucci, Frank Caruso, Francesca Cavalieri

ACS NANO | AMER CHEMICAL SOC | Published : 2019

Abstract

The intracellular delivery of nucleic acids and proteins remains a key challenge in the development of biological therapeutics. In gene therapy, the inefficient delivery of small interfering RNA (siRNA) to the cytosol by lipoplexes or polyplexes is often ascribed to the entrapment and degradation of siRNA payload in the endosomal compartments. A possible mechanism by which polyplexes rupture the endosomal membrane and release their nucleic acid cargo is commonly defined as the "proton sponge effect". This is an osmosis-driven process triggered by the proton buffering capacity of polyplexes. Herein, we investigate the molecular basis of the "proton sponge effect" through direct visualization ..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by National Health and Medical Research Council


Awarded by University of Melbourne Endeavour Research Fellowship - Australian Government, Department of Education and Training


Awarded by ARC Centre of Excellence in Convergent Bio-Nano Science and Technology


Funding Acknowledgements

This work was funded by Australian Research Council (ARC) Future Fellowship (F. Cavalieri FT140100873) and National Health and Medical Research Council Senior Principal Research Fellowship (F. Caruso APP1135806) schemes. This work was also supported by a University of Melbourne Establishment Grant (F. Cavalieri) and an Endeavour Research Fellowship (A. Bertucci no. 5574) granted by the Australian Government, Department of Education and Training. This work was performed at the ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (project number CE140100036). This work was performed in part at the Materials Characterization and Fabrication Platform (MCFP) at The University of Melbourne and the Victorian Node of the Australian National Fabrication Facility (ANFF).