TY - JOUR
T1 - Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells
AU - Beretta, Giovanni L.
AU - Folini, Marco
AU - Cavalieri, Francesca
AU - Yan, Yan
AU - Fresch, Enrico
AU - Kaliappan, Subramanian
AU - Hasenöhrl, Christoph
AU - Richardson, Joseph J.
AU - Tinelli, Stella
AU - Fery, Andreas
AU - Caruso, Frank
AU - Zaffaroni, Nadia
PY - 2015/4/14
Y1 - 2015/4/14
N2 - 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
AB - 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
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U2 - 10.1039/c4nr07240e
DO - 10.1039/c4nr07240e
M3 - Article
C2 - 25779724
AN - SCOPUS:84961291403
VL - 7
SP - 6261
EP - 6270
JO - Nanoscale
JF - Nanoscale
SN - 2040-3364
IS - 14
ER -