Novel Iron Oxide Nanoparticles Induce Ferroptosis in a Panel of Cancer Cell Lines
Roberto Fernández-Acosta,
Claudia Iriarte-Mesa,
Daniel Alvarez-Alminaque,
Behrouz Hassannia,
Bartosz Wiernicki,
Alicia M. Díaz-García,
Peter Vandenabeele,
Tom Vanden Berghe,
Gilberto L. Pardo Andreu
Affiliations
Roberto Fernández-Acosta
Department of Pharmacy, Institute of Pharmaceutical and Food Sciences, University of Havana, 222 Street # 2317, La Coronela, La Lisa, Havana 13600, Cuba
Claudia Iriarte-Mesa
Laboratory of Bioinorganic (LBI), Department of Inorganic and General Chemistry, Faculty of Chemistry, University of Havana, Zapata y G, Vedado, Plaza de la Revolución, Havana 10400, Cuba
Daniel Alvarez-Alminaque
Center for Research and Biological Evaluations, Institute of Pharmaceutical and Food Sciences, University of Havana, 222 Street # 2317, La Coronela, La Lisa, Havana 13600, Cuba
Behrouz Hassannia
VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium
Bartosz Wiernicki
VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium
Alicia M. Díaz-García
Laboratory of Bioinorganic (LBI), Department of Inorganic and General Chemistry, Faculty of Chemistry, University of Havana, Zapata y G, Vedado, Plaza de la Revolución, Havana 10400, Cuba
Peter Vandenabeele
VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium
Tom Vanden Berghe
VIB Center for Inflammation Research (IRC), 9052 Ghent, Belgium
Gilberto L. Pardo Andreu
Center for Research and Biological Evaluations, Institute of Pharmaceutical and Food Sciences, University of Havana, 222 Street # 2317, La Coronela, La Lisa, Havana 13600, Cuba
The use of nanomaterials rationally engineered to treat cancer is a burgeoning field that has reported great medical achievements. Iron-based polymeric nano-formulations with precisely tuned physicochemical properties are an expanding and versatile therapeutic strategy for tumor treatment. Recently, a peculiar type of regulated necrosis named ferroptosis has gained increased attention as a target for cancer therapy. Here, we show for the first time that novel iron oxide nanoparticles coated with gallic acid and polyacrylic acid (IONP–GA/PAA) possess intrinsic cytotoxic activity on various cancer cell lines. Indeed, IONP–GA/PAA treatment efficiently induces ferroptosis in glioblastoma, neuroblastoma, and fibrosarcoma cells. IONP–GA/PAA-induced ferroptosis was blocked by the canonical ferroptosis inhibitors, including deferoxamine and ciclopirox olamine (iron chelators), and ferrostatin-1, the lipophilic radical trap. These ferroptosis inhibitors also prevented the lipid hydroperoxide generation promoted by the nanoparticles. Altogether, we report on novel ferroptosis-inducing iron encapsulated nanoparticles with potent anti-cancer properties, which has promising potential for further in vivo validation.
