Magnetic (Hyper)Thermia or Photothermia? Progressive Comparison of Iron Oxide and Gold Nanoparticles Heating in Water, in Cells, and In Vivo

Magnetic hyperthermia (MHT) and photothermal therapy (PTT) are emergent state‐of‐the‐art modalities for thermal treatment of cancer. While their mechanisms of action have distinct physical bases, both approaches rely on nanoparticle‐mediated remote onset of thermotherapy. Yet, are the two heating techniques interchangeable? Here, the heating obtained either with MHT or with PTT is compared. The heating is assessed in distinct environments and involves a set of nanomaterials differing in shape (spheres, cubes, stars, shells, and rods) as well as in composition (maghemite, magnetite, cobalt ferrite, and gold). The nanoparticle's heating efficacy in an aqueous medium is first evaluated. Subsequently, the heating efficiency within the cellular environment, where intracellular processing markedly decreases MHT, is compared. Conversely, endosomal sequestration could have a positive effect on PTT. Finally, iron oxide nanocubes and gold nanostars are compared in MHT and PTT in vivo within the heterogeneous intratumoral environment. Overall, two distinct therapeutic approaches, related to high dosage allowing MHT and low dosage associated with PTT, are identified. It is also demonstrated that PTT mediated by magnetic nanoparticles has an efficacy that is comparable to that of plasmonic nanoparticles, but only at significant nanoparticle dosages. At low concentrations, only plasmonic nanoparticles can deliver a therapeutic heating. Heat generation is compared for a panel of magnetic and plasmonic nanoparticles, under both magnetic hyperthermia (MHT) and photothermal (PTT) procedures, and in environments of increasing biological complexity. The findings prove that MHT and PTT do not work in the same windows of applicability, and that magnetic nanoparticles are “noble” adversaries to state‐of‐the‐art gold nanoparticles intended for PTT.