Commentary on the clinical and preclinical dosage limits of interstitially administered magnetic fluids for therapeutic hyperthermia based on current practice and efficacy models

<p>We offer a critique of what constitutes a suitable dosage limit, in both clinical and preclinical studies, for interstitially administered magnetic nanoparticles in order to enable therapeutic hyperthermia under the action of an externally applied alternating magnetic field. We approach this first from the perspective of the currently approved clinical dosages of magnetic nanoparticles in the fields of MRI contrast enhancement, sentinel node detection, iron replacement therapy and magnetic thermoablation. We compare this to a simple analytical model of the achievable hyperthermia temperature rise in both humans and animals based on the interstitially administered dose, the heating and dispersion characteristics of the injected fluid, and the strength and frequency of the applied magnetic field. We show that under appropriately chosen conditions a therapeutic temperature rise is achievable in clinically relevant situations. We also show that in such cases it may paradoxically be harder to achieve the same therapeutic temperature rise in a preclinical model. We comment on the implications for the evidence-based translation of hyperthermia based interventions from the laboratory to the clinic.</p

A Direct and Continuous Supercritical Water Process for the Synthesis of Surface-Functionalized Nanoparticles

A new processing methodology is presented for the direct synthesis of surface-functionalized nanoparticles through modification of a single-step continuous supercritical water process. The processing methodology utilizes inexpensive metal salt precursors that form nanoparticles upon mixing the metal salt solution with a supercritical water flow (24 MPa and 450 °C). Surface functionalization is achieved through introducing a supplementary flow of capping agent (citric acid in this example) to the stream of nascent (newly formed) nanoparticles using a novel reactor design. It was found that certain process attributes were key to effective functionalization of the nascent nanoparticle stream, and that high grafting densities of the capping agent were obtained in a relatively narrow process window. We have also used the core design of the reactor to devise and test a scale-up methodology to produce large quantities of surface-functionalized nanoparticles. A method for scaling-up the reactor is described, using a newly developed pilot plant designed to process flow rates 20× greater than the equivalent laboratory-scale process, which yields products at rates of ca. 1 kg/h (effectively semi-industrial-scale production). The method enables large-scale production without recourse to expensive or environmentally damaging reagents and uses water as the only process solvent, a significant advantage over many methods commonly used to produce surface-functionalized nanoparticles. We report the synthesis and characterization of citrate-functionalized Fe₃O₄ nanoparticles as a model system and present detailed characterization of the materials obtained at both processing scales