Redox-active polymer microcapsules for the delivery of a survivin-specific siRNA in prostate cancer cells

Alisa L Becker, Nicola Ivan Orlotti, Marco Folini, Francesca Cavalieri, Alexander N Zelikin, Angus Johnston, Nadia Zaffaroni, Frank Caruso

Research output: Contribution to journalArticleResearchpeer-review

95 Citations (Scopus)

Abstract

In this report, we describe the delivery of small interfering RNA (siRNA) using LbL-assembled microcapsules. The microcapsules are based on negatively charged poly(methacrylic acid) nanometer thin films containing cross-linking disulfide bonds. One system is polycation-free and another contains polylysine for siRNA complexation in the microcapsule void. When microcapsules containing a siRNA targeting survivin were delivered to PC-3 prostate cancer cells, a significant inhibition of the expression of the antiapoptotic protein was observed. However, down-regulation of survivin was also observed in PC-3 cells exposed to microcapsules embedded with a scrambled siRNA as well as in cells treated with empty microcapsules. These findings indicate a capsule-dependent off-target effect, which is supported by a reduction in the expression of other survivin-unrelated proteins. The microcapsules and their polymeric constituents do not affect cell proliferation, as determined by a metabolic assay, even after 4 days of exposure. In addition, in PC-3 cells exposed to microcapsules, we observed a marked accumulation of LC3b, a marker related to autophagy (i.e., self-digestion), a degradation pathway involved in the maintenance of cell homeostasis in response to different stresses. This evidence suggests that empty microcapsules can induce a perturbation of the intracellular environment, which causes the activation of a cell safeguard mechanism that may limit the therapeutic effect of the microcapsules in tumor cells.
Original languageEnglish
Pages (from-to)1335 - 1344
Number of pages10
JournalACS Nano
Volume5
Issue number2
DOIs
Publication statusPublished - 2011
Externally publishedYes

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