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

Beretta GL, Folini M, Cavalieri F, Yan Y, Fresch E, Kaliappan S, Hasenhoerl C, Richardson JJ, Tinelli S, Fery A, Caruso F, Zaffaroni N (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Nanoscale Royal Society of Chemistry

Book Volume: 7

Pages Range: 6261-6270

Journal Issue: 14

DOI: 10.1039/c4nr07240e

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. This journal is

Involved external institutions

Fondazione IRCCS: Istituto Nazionale dei Tumori IT Italy (IT) Università degli Studi di Roma 'Tor Vergata' IT Italy (IT) The University of Melbourne AU Australia (AU) Universität Bayreuth DE Germany (DE)

How to cite

APA:

Beretta, G.L., Folini, M., Cavalieri, F., Yan, Y., Fresch, E., Kaliappan, S.,... Zaffaroni, N. (2015). Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells. Nanoscale, 7(14), 6261-6270. https://dx.doi.org/10.1039/c4nr07240e

MLA:

Beretta, Giovanni L., et al. "Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells." Nanoscale 7.14 (2015): 6261-6270.

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