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

Giovanni L. Beretta, Marco Folini, Francesca Cavalieri, Yan Yan, Enrico Fresch, Subramanian Kaliappan, Christoph Hasenöhrl, Joseph J. Richardson, Stella Tinelli, Andreas Fery, Frank Caruso, Nadia Zaffaroni

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish
Pages (from-to)6261-6270
Number of pages10
JournalNanoscale
Volume7
Issue number14
DOIs
Publication statusPublished - Apr 14 2015

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint Dive into the research topics of 'Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells'. Together they form a unique fingerprint.

Cite this