Pt(IV)-functionalised polyacrylic acid-coated iron oxide magnetic nanoparticles as redox-responsive cancer theranostics.

Iron oxide nanoparticles represent a class of nanomaterials with unique physicochemical properties and high potential for theranostic applications. Herein, we functionalised polyacrylic acid (PAA)-coated iron oxide nanoparticles with a chemotherapeutic Pt(IV) prodrug, to prepare Fe3O4@PAA-Pt(IV) nanostructures that act as T2 MR theranostics with redox- (and thus TME-) responsive therapeutic properties. The synthesis of Fe3O4@PAA-Pt(IV) nanoparticles was optimised to yield nanoparticles with appropriate hydrodynamic diameter and Pt/Fe ratio. The Fe3O4@PAA-Pt(IV) nanoparticles displayed promising magnetic and relaxometric properties, showing a higher relaxivity than commercially available NP-based MRI agent Resovist®. Cell internalisation studies in 2D and 3D cell models demonstrated that the nanomaterials accumulated in cancer cells after only 6 h of incubation at a concentration that allowed for contrast enhancement in MRI. Cell viability studies showed that Fe3O4@PAA-Pt(IV) nanoparticles were 2.5 times more effective than the Pt(IV) prodrug in inducing apoptosis (IC50 = 156 μM vs. 379 μM) in 2D models, while in 3D models, they were found to be as effective as active drug cisplatin. These results show the potential of these versatile Pt(IV)-functionalised PAA-coated iron oxide nanostructures as redox responsive MR theranostics for cancer therapy.