ROS-Mediated Apoptosis and Anticancer Effect Achieved by Artesunate and Auxiliary Fe(II) Released from Ferriferous Oxide-Containing Recombinant Apoferritin

Reactive oxygen species (ROS)-mediated apoptosis is considered a crucial therapeutic mechanisms for artesunate (AS). As an Fe(II)-dependent drug, the anticancer effect of AS is often limited due to insufficient Fe(II) concentration in targeted cells. To overcome this problem, a recombinant apoferritin nanocarrier containing ferriferous oxide (M-HFn) is constructed to produce auxiliary exogenous Fe(II) when delivering AS to cancer cells. Here, the newly fabricated AS-loaded M-HFn nanoparticles (M-HFn@AS NPs) can significantly improve the tumor-specific targeting and intracellular uptake efficiency of AS in human cervical carcinoma cells. After being captured in the acidic cavity of endosomes, M-HFn@AS NPs can simultaneously release Fe(II) and allow AS to activate satisfactory ROS-mediated apoptosis. Furthermore, in vivo studies demonstrate that M-HFn@AS NPs can selectively accumulate in tumors to efficiently inhibit tumor growth. Thus, M-HFn@AS NPs are a promising system to enhance the therapeutic effect of Fe(II)-dependent drugs.