Magnetic nanoparticles, (MNP), are the building-blocks for developing innovative nanodevices with multi-fold therapeutic and diagnostic activities, including magnetic fluid hyperthermia, (MFH), contrast agents for Magnetic Resonance Imaging, (CA-MRI), and targeting of tumor cells. Among the different functionalization strategies developed so far, the approaches using protein-cage structures, like those of the ferritin (Ft) family, are particularly promising, since Fts present a number of favorable properties: they have high solubility and stability in water, blood and buffers, low toxicity, and they can be easily functionalized through genetic engineering and/or chemical reactions involving one of the many chemical groups exposed to the exterior (primary amines, carboxylates, thiols).
In this contribution we present some examples of the application of a human H chain ferritin, HFt, for the realization of magnetic-based theranostic agents for the treatment of melanoma. We will show how, through the fine tuning of the composition of the ferrite nucleus grown within the proteic shell of HFt, this system can become an efficient heat mediator in the tumor treatment via MFH. Indeed, the main constraint of HFt-based MNPs is that their size cannot exceed the protein shell inner diameter (ca. 8 nm). As far as iron oxide is concerned, this size is large enough for MRI application, but it is too small for MFH, as theoretical and experimental studies demonstrated that the maximum MFH efficiency is reached for magnetite MNP of d=16-18 nm, while very poor effects are expected for d<10 nm.
In particular, we will focus on highly monodisperse doped iron oxides NPs mineralized inside a genetically modified variant of HFt, carrying several copies of alfa-melanocyte-stimulating hormone peptide, which has excellent targeting properties towards melanoma cells with high selectivity, and conjugated to polyethylene glycol molecules to increase their in vivo stability.
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