Combination of cerium oxide nanoparticles and antimalarial drug chloroquine: characterization and anti-cancer potential for triple negative breast cancer

• Chloroquine (CQ) does not restrict cerium oxide nanoparticles (CNP) functionality. • CNP/CQ combination selectively decreased the viability of triple negative breast cancer (TNBC) monolayers. • CNP/CQ combination selectively decreased the viability of TNBC spheroids. • Combination of CNP and CQ is more effective than the single treatments. • Combining CNP and CQ lowered the individual doses while maintaining treatment efficacy. Triple negative breast cancer (TNBC) is highly aggressiveness, has a poor prognosis, and standard therapy is often associated with adverse effects. As drug repurposing and nanomedicine have gained huge interest in cancer therapy, the effect of the antimalarial drug chloroquine (CQ) in combination with cerium oxide nanoparticles (CNP) was tested as an alternative approach for the selective treatment of TNBC. Initially, functional characterization of the novel combination was performed using e.g. X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), high-resolution transmission electron microscopy (HR-TEM), and a superoxide dismutase (SOD) activity assay. Cellular uptake, therapeutic efficacy, and selectivity of the combination were confirmed in a 2D in vitro model using MDA-MB-231 and MDA-MB-468 TNBC cells and normal (healthy) MCF12A breast epithelial cells. To translate our novel findings into a more in vivo situation, the anti-cancer effect of CNP/CQ was also demonstrated in a 3D spheroid model. CNP and CQ selectively decreased the viability of tumor spheroids without harming MCF-12A spheroids. For the first time, our study indicates that a combination of CNP and CQ may be a beneficial alternative treatment for TNBC in the future.