Fenton-Reaction-Acceleratable Magnetic Nanoparticles for Ferroptosis Therapy of Orthotopic Brain TumorsстатьяИсследовательская статья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 11 января 2019 г.
Аннотация:Cancer is one of the leading causes of morbidity and mortality
in the world, but more cancer therapies are needed to complement existing
regimens due to problems of existing cancer therapies. Herein, we term
ferroptosis therapy (FT) as a form of cancer therapy and hypothesize that the
FT efficacy can be significantly improved via accelerating the Fenton reaction
by simultaneously increasing the local concentrations of all reactants (Fe2+,
Fe3+, and H2O2) in cancer cells. Thus, Fenton-reaction-acceleratable
magnetic nanoparticles, i.e., cisplatin (CDDP)-loaded Fe3O4/Gd2O3 hybrid
nanoparticles with conjugation of lactoferrin (LF) and RGD dimer (RGD2)
(FeGd-HN@Pt@LF/RGD2), were exploited in this study for FT of
orthotopic brain tumors. FeGd-HN@Pt@LF/RGD2 nanoparticles were
able to cross the blood−brain barrier because of its small size (6.6 nm) and LF-receptor-mediated transcytosis. FeGd-
HN@Pt@LF/RGD2 can be internalized into cancer cells by integrin αvβ3-mediated endocytosis and then release Fe2+,
Fe3+, and CDDP upon endosomal uptake and degradation. Fe2+ and Fe3+ can directly participate in the Fenton reaction,
whereas the CDDP can indirectly produce H2O2 to further accelerate the Fenton reaction. The acceleration of Fenton
reaction generates reactive oxygen species to induce cancer cell death. FeGd-HN@Pt@LF/RGD2 successfully delivered
reactants involved in the Fenton reaction to the tumor site and led to significant inhibition of tumor growth. Finally, the
intrinsic magnetic resonance imaging (MRI) capability of the nanoparticles was used to assess and monitor tumor
response to FT (self-MRI monitoring).