Unravelling "off-target" effects of redox-active polymers and polymer multilayered capsules in prostate cancer cells
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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.
Details
Originalsprache | Englisch |
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Seiten (von - bis) | 6261-6270 |
Seitenumfang | 10 |
Fachzeitschrift | Nanoscale |
Jahrgang | 7 |
Ausgabenummer | 14 |
Publikationsstatus | Veröffentlicht - 14 Apr. 2015 |
Peer-Review-Status | Ja |
Extern publiziert | Ja |
Externe IDs
PubMed | 25779724 |
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