Multifunctional nanoparticles that carry chemotherapeutic agents can be innovative anticancer therapeutic options owing to their
tumor-targeting ability and high
drug-loading capacity. However, the nonspecific release of toxic
DNA-intercalating anticancer drugs from the nanoparticles has significant side effects on healthy cells surrounding the
tumors. Herein, we report a
tumor homing
reactive oxygen species nanoparticle (THoR-NP) platform that is highly effective and selective for ablating malignant
tumors.
Sodium nitroprusside (SNP) and
diethyldithiocarbamate (DDC) were selected as an exogenous
reactive oxygen species (ROS) generator and a
superoxide dismutase 1 inhibitor, respectively. DDC-loaded THoR-NP, in combination with SNP treatment, eliminated multiple
cancer cell lines effectively by the generation of
peroxynitrite in the cells (>95% cell death), as compared to control drug treatments of the same concentration of DDC or SNP alone (0% cell death). Moreover, the magnetic core (ZnFe2O4) of the THoR-NP can specifically ablate
tumor cells (
breast cancer cells) via magnetic
hyperthermia, in conjunction with DDC, even in the absence of any exogenous RS supplements. Finally, by incorporating
iRGD peptide moieties in the THoR-NP,
integrin-enriched
cancer cells (malignant tumors, MDA-MB-231) were effectively and selectively killed, as opposed to nonmetastatic
tumors (MCF-7), as confirmed in a mouse xenograft model. Hence, our strategy of using nanoparticles embedded with ROS-scavenger-inhibitor with an exogenous ROS supplement is highly selective and effective
cancer therapy.