Theranostic Nanoparticles for MRI-Guided Thermochemotherapy: "Tight" Clustering of Magnetic Nanoparticles Boosts Relaxivity and Heat-Generation Power.

Magnetic-resonance-imaging (MRI)-guided magnetic thermochemotherapy is a potentially invasive technique combining diagnosis and treatment. It requires the development of multifunctional nanoparticles with (1) biocompatibility, (2) high relaxivity, (3) high heat-generation power, (4) controlled drug release, and (5) tumor targeting. Here, we show the synthesis of such multifunctional nanoparticles ("Core-Shells") and the feasibility of MRI-guided magnetic thermochemotherapy using the synthesized nanoparticles. "Tight" iron-oxide nanoparticle clustering to zero interparticle distance within the Core-Shells boosts the relaxivity and heat-generation power while maintaining biocompatibility. The initial Core-Shell drug release occurs in response to an alternating magnetic field (AMF) and continues gradually after removal of the AMF. Thus, a single Core-Shell dose realizes continuous chemotherapy over a period of days or weeks. The Core-Shells accumulate in abdomen tumors, facilitating MRI visualization. Subsequent AMF application induces heat generation and drug release within the tumors, inhibiting their growth. Core-Shell magnetic thermochemotherapy exhibits significantly higher therapeutic efficacy than both magnetic hyperthermia and chemotherapy alone. More importantly, there are minimal side effects. The findings of this study introduce new perspectives regarding the development of materials for MRI, magnetic hyperthermia, and drug delivery systems. Both conventional and novel iron-oxide-based materials may render theranostics (i.e., techniques fusing diagnosis and treatment) feasible.