Pt(<scp>iv</scp>)-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 <i>T</i>₂ 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 <i>vs.</i> 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.