A Smart Platform for Hyperthermia Application in Cancer Treatment: Cobalt-Doped Ferrite Nanoparticles Mineralized in Human Ferritin Cages

Abstract

Magnetic nanoparticles, MNPs, mineralized within a human ferritin protein cage, HFt, can represent an appealing platform to realize smart therapeutic agents for cancer treatment by drug delivery and magnetic fluid hyperthermia, MFH. However, the constraint imposed by the inner diameter of the protein shell (ca. 8 nm) prevents its use as heat mediator in MFH when the MNPs comprise pure iron oxide. In this contribution, we demonstrate how this limitation can be overcome through the controlled doping of the core with small amount of Co(II). Highly monodisperse doped iron oxide NPs with average size of 7 nm are mineralized inside a genetically modified variant of HFt, carrying several copies of α-melanocyte-stimulating hormone peptide, which has already been demonstrated to have excellent targeting properties toward melanoma cells. HFt is also conjugated to poly(ethylene glycol) molecules to increase its in vivo stability. The investigation of hyperthermic properties of HFt-NPs shows that a Co doping of 5% is enough to strongly enhance the magnetic anisotropy and thus the hyperthermic efficiency with respect to the undoped sample. In vitro tests performed on B16 melanoma cell line demonstrate a strong reduction of the cell viability after treatment with Co doped HFt-NPs and exposure to the alternating magnetic field. Clear indications of an advanced stage of apoptotic process is also observed from immunocytochemistry analysis. The obtained data suggest this system represents a promising candidate for the development of a protein-based theranostic nanoplatform.

Intra- and interparticle magnetism of cobalt-doped iron-oxide nanoparticles encapsulated in a synthetic ferritin cage

“…No variation in the line broadening between samples was observed that indicated that the addition of cobalt did not affect the crystallinity or particle size as has been observed in some other cases using traditional solution synthesis of other ferritins 13,14 . This was consistent with the previously observed characteristics of PfFt in providing a favourable environment for the efficient formation of well crystallized nanoparticles 10 , and facilitates a comparison of the intrinsic magnetism.…”

Hybrid Nanomaterials by Surface Grafting of Synthetic Polypeptides Using N‐Carboxyanhydride (NCA) Polymerization

“…[61][62][63] In recent years, attempts have been made to enhance their properties and to impart unique functionalities to these nanomaterials by employing surface-initiated NCA polymerization. Yang and co-workers prepared magnetic-silica polypeptide hybrids by polymerizing NCA-BLG from the nanoparticle surface.…”

Nanoscale device architectures derived from biological assemblies: The case of tobacco mosaic virus and (apo)ferritin

“…The N-termini of the subunits are positioned on the external protein surface near the threefold axis, which is a very suitable position to introduce additional functionalities such as for mineralization, 42,43) crystallization, 44,45) and cell recognition. 40,46,47) The C-termini point towards the cavity on the fourfold symmetry axis and can be used to generate nucleation points for mineral growth. 48) Mutations in the ferroxidase catalytic centers and at the nucleation sites have been generated to study iron metabolism.…”

“…For example, magnetic Fe 3 O 4 75) 41,[84][85][86][87] for magnetic resonance imaging, 32,46) and even as the core of a magnonic device. 88) In analogy, Co(O)OH 89) 91) Many metal hydroxide NPs can be grown from the respective metal ion without an oxidizer.…”