Redox-sensitive PEG-polypeptide nanoporous particles for survivin silencing in prostate cancer cells

F Cavalieri; GL Beretta; J Cui; JA Braunger; Y Yan; JJ Richardson; S Tinelli; M Folini; N Zaffaroni; F Caruso

Journal article

Redox-sensitive PEG-polypeptide nanoporous particles for survivin silencing in prostate cancer cells

F Cavalieri, GL Beretta, J Cui, JA Braunger, Y Yan, JJ Richardson, S Tinelli, M Folini, N Zaffaroni, F Caruso

Biomacromolecules | Published : 2015

DOI: 10.1021/acs.biomac.5b00562

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Abstract

We report the engineering of intracellular redox-responsive nanoporous poly(ethylene glycol)-poly(l-lysine) particles (NPEG-PLLs). The obtained particles exhibit no toxicity while maintaining the capability to deliver a small interfering RNA sequence (siRNA) targeting the anti-apoptotic factor, survivin, in prostate cancer cells. The redox-mediated cleavage of the disulfide bonds stabilizing the NPEG-PLL-siRNA complex results in the release of bioactive siRNA into the cytosol of prostate cancer PC-3 cells, which, in turn, leads to the effective silencing (∼59 ± 8%) of the target gene. These findings, obtained under optimal conditions, indicate that NPEG-PLLs may protect the therapeutic nucle..

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University of Melbourne Researchers

Francesca Cavalieri Author

Frank Caruso Author

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Awarded by European Commission

Funding Acknowledgements

This work was supported in part by grants from the Marie Curie Actions-International Research Staff Exchange Scheme (grant no. 247542, Nanosirna), Fondazione Italo Monzino, and the Australian Research Council (ARC) under the Australian Laureate Fellowship (F. Caruso, FL120100030), Super Science Fellowship (F. Caruso, FS110200025), ARC Centre of Excellence in Convergent Bio-Nano Science and Technology (project no. CE140100036), and Future Fellowship 2014 (F. Cavalieri FT140100873) schemes. The authors thank Benjamin Hibbs and Matthew Faria for providing assistance in the use of SIM and Protein Data Bank, respectively. This work was performed in part at the Materials Characterisation and Fabrication Platform (MCFP) at The University of Melbourne.