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Issue 14, 2015
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Unravelling “off-target” effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

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Abstract

Redox-active polymers and carriers are oxidizing nanoagents that can potentially trigger intracellular off-target effects. In the present study, we investigated the occurrence of off-target effects in prostate cancer cells following exposure to redox-active polymer and thin multilayer capsules with different chemical properties. We show that, depending on the intracellular antioxidant capacity, thiol-functionalized poly(methacrylic acid), PMASH triggers cell defense responses/perturbations that result in off-target effects (i.e., induction of autophagy and down-regulation of survivin). Importantly, the conversion of the carboxyl groups of PMASH into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMASH) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMASH polymer or capsules may play a role in mediating the intracellular off-target effects. Our work provides evidence that the rational design of redox-active carriers for therapeutic-related application should be guided by a careful investigation on potential disturbance of the cellular machineries related to the carrier association.

Graphical abstract: Unravelling “off-target” effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

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Supplementary files

Article information


Submitted
08 Dec 2014
Accepted
04 Mar 2015
First published
17 Mar 2015

This article is Open Access

Nanoscale, 2015,7, 6261-6270
Article type
Paper

Unravelling “off-target” effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells

G. L. Beretta, M. Folini, F. Cavalieri, Y. Yan, E. Fresch, S. Kaliappan, C. Hasenöhrl, J. J. Richardson, S. Tinelli, A. Fery, F. Caruso and N. Zaffaroni, Nanoscale, 2015, 7, 6261
DOI: 10.1039/C4NR07240E

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