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

作者：Beretta Giovanni L; Folini Marco; Cavalieri Francesca; Yan Yan; Fresch Enrico; Kaliappan Subramanian; Hasenhoerl Christoph; Richardson Joseph J; Tinelli Stella; Fery Andreas; Caruso Frank^*; Zaffaroni Nadia

来源：Nanoscale, 2015, 7(14): 6261-6270.

DOI：10.1039/c4nr07240e

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.

• 出版日期2015