Journal article

Glycogen-nucleic acid constructs for gene silencing in multicellular tumor spheroids

Marcin Wojnilowicz, Quinn A Besford, Yun-Long Wu, Xian Jun Loh, Julia A Braunger, Agata Glab, Christina Cortez-Jugo, Frank Caruso, Francesca Cavalieri

BIOMATERIALS | ELSEVIER SCI LTD | Published : 2018

Abstract

The poor penetration of nanocarrier-siRNA constructs into tumor tissue is a major hurdle for the in vivo efficacy of siRNA therapeutics, where the ability of the constructs to permeate the 3D multicellular matrix is determined by their physicochemical properties. Herein, we optimized the use of soft glycogen nanoparticles for the engineering of glycogen-siRNA constructs that can efficiently penetrate multicellular tumor spheroids and exert a significant gene silencing effect. Glycogen nanoparticles from different bio-sources and with different structural features were investigated. We show that larger glycogen nanoparticles ranging from 50 to 80 nm are suboptimal systems for complexation of ..

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Grants

Awarded by Australian Research Council (ARC)


Awarded by Australian Laureate Fellowship


Awarded by NHMRC Fellowship


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


Funding Acknowledgements

This work was supported by the Australian Research Council (ARC) under Future Fellowship (F. Cavalieri, FT140100873), Australian Laureate Fellowship (F. Caruso, FL120100030) schemes and NHMRC Fellowship (F. Caruso, APP1135806). This work was also supported by a University of Melbourne Establishment Grant (F. Cavalieri). This research was conducted by 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, the Victorian Node of the Australian National Fabrication Facility (ANFF), and the SAXS/WAXS beamline of the Australian Synchrotron, Victoria, Australia (11587). We thank Laura Leone for assistance with microtome sectioning.