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

Francesca Cavalieri, Giovanni L. Beretta, Jiwei Cui, Julia A. Braunger, Yan Yan, Joseph J. Richardson, Stella Tinelli, Marco Folini, Nadia Zaffaroni, Frank Caruso

Research output: Contribution to journalArticle

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 nucleic acid in the extracellular and intracellular environments, thus preventing the occurrence of competitive interactions with serum and cytosolic proteins as well as degradation by RNase. The intracellular trafficking and final fate of the NPEG-PLLs were investigated by a combination of deconvolution microscopy, fluorescence lifetime imaging microscopy, and super-resolution structured illumination microscopy. A significant impairment of cell survival was observed in cells concomitantly exposed to paclitaxel and siRNA-loaded NPEG-PLLs. Overall, our findings indicate that NPEG-PLLs represent a highly loaded depot for the delivery of therapeutic nucleic acids to cancer cells.

Original languageEnglish
Pages (from-to)2168-2178
Number of pages11
JournalBiomacromolecules
Volume16
Issue number7
DOIs
Publication statusPublished - Jul 13 2015

ASJC Scopus subject areas

  • Bioengineering
  • Materials Chemistry
  • Polymers and Plastics
  • Biomaterials

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  • Cite this

    Cavalieri, F., Beretta, G. L., Cui, J., Braunger, J. A., Yan, Y., Richardson, J. J., Tinelli, S., Folini, M., Zaffaroni, N., & Caruso, F. (2015). Redox-sensitive PEG-polypeptide nanoporous particles for survivin silencing in prostate cancer cells. Biomacromolecules, 16(7), 2168-2178. https://doi.org/10.1021/acs.biomac.5b00562