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), PMA(SH) 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 PMA(SH) into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMA(SH)) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMA(SH) 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.

Beretta, G.l., Folini, M., Cavalieri, F., Yan, Y., Fresch, E., Kaliappan, S., et al. (2015). Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells. NANOSCALE, 7(14), 6261-6270 [10.1039/c4nr07240e].

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

CAVALIERI, FRANCESCA;
2015

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), PMA(SH) 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 PMA(SH) into the neutral amides of poly(hydroxypropylmetacrylamide) (pHPMA(SH)) nullified the off-target effects and cytotoxicity in tested cell lines. This suggests that the simultaneous action of carboxyl and disulfide groups in PMA(SH) 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.
Pubblicato
Rilevanza nazionale
Articolo
Esperti anonimi
Settore CHIM/02 - Chimica Fisica
English
Con Impact Factor ISI
Capsules; Cell Line, Tumor; Humans; Male; Oxidation-Reduction; Prostatic Neoplasms; Acrylamides; Antioxidants; Materials Testing; Polymethacrylic Acids
Beretta, G.l., Folini, M., Cavalieri, F., Yan, Y., Fresch, E., Kaliappan, S., et al. (2015). Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells. NANOSCALE, 7(14), 6261-6270 [10.1039/c4nr07240e].
Beretta, G; Folini, M; Cavalieri, F; Yan, Y; Fresch, E; Kaliappan, S; Hasenohrl, C; Richardson, J; Tinelli, S; Fery, A; Caruso, F; Zaffaroni, N
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/149088
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