Physiological Remediation of Cobalt Ferrite Nanoparticles by Ferritin

Abstract

Metallic nanoparticles have been increasingly suggested as prospective therapeutic nanoplatforms, yet their long-term fate and cellular processing in the body is poorly understood. Here we examined the role of an endogenous iron storage protein – namely the ferritin – in the remediation of biodegradable cobalt ferrite magnetic nanoparticles. Structural and elemental analysis of ferritins close to exogenous nanoparticles within spleens and livers of mice injected in vivo with cobalt ferrite nanoparticles, suggests the intracellular transfer of degradation-derived cobalt and iron, entrapped within endogenous protein cages. In addition, the capacity of ferritin cages to accommodate and store the degradation products of cobalt ferrite nanoparticles was investigated in vitro in the acidic environment mimicking the physiological conditions that are present within the lysosomes. The magnetic, colloidal and structural follow-up of nanoparticles and proteins in the lysosome-like medium confirmed the efficient remediation of nanoparticle-released cobalt and iron ions by ferritins in solution. Metal transfer into ferritins could represent a quintessential process in which biomolecules and homeostasis regulate the local degradation of nanoparticles and recycle their by-products.

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

“…[ 19 ] Meanwhile, CoFe 2 O 4 nanoparticles are biodegradable in the acidic environment of lysosomes and metabolized by liver and spleen, resulting in acceptable biocompatibility even at a concentration of 5.87 mg kg −1 in mice. [ 20 ] Considering the long‐term monitoring requirements, minimal toxicity, and minimal impact on hydrogel degradation, the MNPs with a concentration of 0.34 mg kg −1 (68 µg mL −1 ) were encapsulated into the PLGA‐PEG‐PLGA hydrogel to increase its contrast with the adjacent tissues during in vivo degradation.…”

Exploiting Unique Alignment of Cobalt Ferrite Nanoparticles, Mild Hyperthermia, and Controlled Intrinsic Cobalt Toxicity for Cancer Therapy

“…This localization can potentially promote degradation of these nanocubes at acidic endosomal pH, particularly in the case of Co–Fe NCs releasing toxic cobalt within the tumor cells, leading to their destruction. [ 16,17 ] Also, the groups treated with IONCs and IONCs + HT did not show any unique alignment of nanocubes (Figure 3a,b). Unexpectedly the Co–Fe NCs structures found within the tumors, both with and without HT, were forming chain‐like alignments (Figure 3c,d).…”

“…The uptaken cobalt ferrite nanoparticles can undergo degradation within lysosome, at acidic pH, leading to slow etching and release of the included cobalt ions. [ 16,17 ] In fact, heavy metals and toxic elements are already in use in clinical chemotherapy. [ 18 ] Instead of using a separate cytotoxic agent, the use of Co–Fe NPs could potentiate delivery of toxic Co ions, as a form of chemotherapy to tumor cells.…”

3D‐Printed Soft Magnetoelectric Microswimmers for Delivery and Differentiation of Neuron‐Like Cells

“…Intracellular ferritin cages localized nearby the nanoparticles could act as storage proteins for the metal ions released during the degradation. [ 14 ] These preliminary studies show promising application of the MENPs as a therapeutic agent. Note that further investigations are required to assess the long‐term in vivo biosafety of MENPs, although these MENPs did not show acute toxicity under the investigated conditions.…”