pH-Responsive, Self-Sacrificial Nanotheranostic Agent for Potential In Vivo and In Vitro Dual Modal MRI/CT Imaging, Real-Time, and In Situ Monitoring of Cancer Therapy.

ABSTRACT

Multifunctional nanotheranostic agents have been highly commended due to the application to image-guided cancer therapy. Herein, based on the chemically disordered face centered cubic (fcc) FePt nanoparticles (NPs) and graphene oxide (GO), we develop a pH-responsive FePt-based multifunctional theranostic agent for potential in vivo and in vitro dual modal MRI/CT imaging and in situ cancer inhibition. The fcc-FePt will release highly active Fe ions due to the low pH in tumor cells, which would catalyze H2O2 decomposition into reactive oxygen species (ROS) within the cells and further induce cancer cell apoptosis. Conjugated with folic acid (FA), the iron platinum-dimercaptosuccinnic acid/PEGylated graphene oxide-folic acid (FePt-DMSA/GO-PEG-FA) composite nanoassemblies (FePt/GO CNs) could effectively target and show significant toxicity to FA receptor-positive tumor cells, but no obvious toxicity to FA receptor-negative normal cells, which was evaluated by WST-1 assay. The FePt-based multifunctional nanoparticles allow real-time monitoring of Fe release by T2-weighted MRI, and the selective contrast enhancement in CT could be estimated in vivo after injection. The results showed that FePt-based NPs displayed excellent biocompatibility and favorable MRI/CT imaging ability in vivo and in vitro. Meanwhile, the decomposition of FePt will dramatically decrease the T2-weighted MRI signal and increase the ROS signal, which enables real-time and in situ visualized monitoring of Fe release in tumor cells. In addition, the self-sacrificial decomposition of fcc-FePt will be propitious to the self-clearance of the as-prepared FePt-based nanocomposite in vivo. Therefore, the FePt/GO CNs could serve as a potential multifunctional theranostic nanoplatform of MRI/CT imaging guided cancer diagnosis and therapy in the clinic.