pH-Responsive magnetic nanocarriers for chelator-free bimodal (MRI/SPECT-CT) image-guided chemo-hyperthermia therapy in human breast carcinoma.

Although chemotherapy with magnetic nanocarriers has witnessed significant advancement in the field of cancer treatment, multimodal diagnosis and combinatorial therapy using a single nanoplatform will have much better efficacy in achieving superior results. Herein, we constructed a smart theranostic system by combining pH-sensitive tartaric acid-stabilized FeO magnetic nanocarriers (TMNCs) with SPECT imaging and a chemotherapeutic agent for image-guided chemo-hyperthermia therapy. The carboxyl-enriched exteriors of TMNCs provided sites for the conjugation of a chemotherapeutic drug (doxorubicin hydrochloride, DOX) and radiolabeling (Ce). The usage of 145.4 keV gamma rays made this platform an ideal choice for SPECT-CT imaging, showing the retention of the nanoformulation in the tumor site even after 28 days. Further, TMNCs showed a very high transverse relaxation rate () of 171 mM s, which is higher than that of clinically approved magnetic resonance imaging (MRI) contrast agents such as ferumoxtran (65 mM s) and ferumoxides (120 mM s). Further, the developed drug-loaded hybrid platform showed significantly higher cytotoxicity towards breast cancer cells, which was augmented by magnetic hyperthermia. Bright-field microscopy and cell cycle analysis suggested that cell death occurred through induction of G2-M arrest and subsequent apoptosis. These findings clearly suggest the potential of the developed hybrid nanoplatform for image-guided combination therapy.