Long-Term Fate of Magnetic Particles in Mice: A Comprehensive Study

Abstract

Safe application of nanoparticles in medicine requires full understanding of their pharmacokinetics including catabolism in the organism. However, information about nanoparticle degradation is still scanty due to difficulty of long-term measurements by invasive techniques. Here, we describe a magnetic spectral approach for in vivo monitoring of magnetic particle (MP) degradation. The method noninvasiveness has allowed performing of a broad comprehensive study of the 1-year fate of 17 types of iron oxide particles. We show a long-lasting influence of five parameters on the MP degradation half-life: dose, hydrodynamic size, ζ-potential, surface coating, and internal architecture. We observed a slowdown in MP biotransformation with an increase of the injected dose and faster degradation of the particles of a small hydrodynamic size. A comparison of six types of 100 nm particles coated by different hydrophilic polymer shells has shown that the slowest (t 1/2 = 38 ± 6 days) and the fastest (t 1/2 = 15 ± 4 days) degradations were achieved with a polyethylene glycol and polyglucuronic acid coatings, respectively. The most significant influence on the MP degradation was due to the internal architecture of the particles as the coverage of magnetic cores with a solid 39 nm polystyrene layer slowed down the half-life of the core−shell MPs from 48 days to more than 1 year. The revealed deeper insights into the particle degradation in vivo may facilitate rational design of nano-and microparticles with predictable long-term fate in vivo.

The Effect of pH and Buffer on Oligonucleotide Affinity for Iron Oxide Nanoparticles

“…Therefore, it is essential to consider the functionalization of such MNPs with polymers. The wrong functionalization leads to instability in biological liquids, toxicity, and high reactive oxygen species formation in cell lines and animal models [2,4,[21][22][23][24]. The modified coatings improve the stability, aggregation properties, and biocompatibility of naked Fe 3 O 4 MNPs.…”

Nanoparticles for Magnetic Heating: When Two (or More) Is Better Than One

“…However, biocompatibility and safety constraints reduce the degrees of freedom. This aspect is crucial and, due to the increasing use of NPs in biomedicine, elucidating their interaction with the biological environment, both in vitro and in vivo conditions, as well as their fate in living organisms is currently a hot research topic [ 268 , 269 , 270 , 271 ], albeit beyond the scope of this review article. It is to be expected that the concerns about biosafety and long-term distribution of the NPs in the patient’s body will further push the search for innovative nanoheaters and lead to the creation of increasingly versatile magnetic architectures able to combine tunable heating efficiency with assessed biodegradation and clearance properties.…”

Magnetofection In Vivo by Nanomagnetic Carriers Systemically Administered into the Bloodstream

“…That causes rapid plasma clearance of the nanocarriers leading to short nanoparticle plasma half-life [102]. Therefore, it is necessary to study in detail the issues related to the factors that affect blood circulation [8,103], as well as elimination [104,105] of nanoparticles for successful applications of in vivo magnetofection, search for new hybrid delivering nanomaterials [106][107][108][109] or implementation of more efficient biochemical binding and targeting techniques [110][111][112][113][114][115][116]. However, we believe that the magnetofection technique can become a solid option for in vivo targeting combined with improved efficacy of gene delivery, potentially in combination with other physical techniques (electroporation, sonoporation) if appropriate magnetic fields can be generated and if an ideal coating of magnetic particles is found.…”