Synthesis and modification of uniform PEG-neridronate-modified magnetic nanoparticles determines prolonged blood circulation and biodistribution in a mouse preclinical model

Abstract

Magnetite (Fe 3 O 4 ) nanoparticles with uniform sizes of 10, 20, and 31 nm were prepared by thermal decomposition of Fe(III) oleate or mandelate in a high-boiling point solvent (>320 °C). To render the particles with hydrophilic and antifouling properties, their surface was coated with a PEG-containing bisphosphonate anchoring group. The PEGylated particles were characterized by a range of physicochemical methods, including dynamic light scattering, transmission electron microscopy, thermogravimetric analysis, Fourier transform infrared spectroscopy, and magnetization measurements. As the particle size increased from 10 to 31 nm, the amount of PEG coating decreased from 28.5 to 9 wt.%. The PEG formed a dense brush-like shell on the particle surface, which prevented particles from aggregating in water and PBS (pH 7.4) and maximized the circulation time in vivo . Magnetic resonance relaxometry confirmed that the PEG-modified Fe 3 O 4 nanoparticles had high relaxivity, which increased with increasing particle size. In the in vivo experiments in a mouse model, the particles provided visible contrast enhancement in the magnetic resonance images. Almost 70% of administrated 20-nm magnetic nanoparticles still circulated in the blood stream after four hours; however, their retention in the tumor was rather low, which was likely due to the antifouling properties of PEG.

The Effect of Surface Coating of Iron Oxide Nanoparticles on Magnetic Resonance Imaging Relaxivity

“…The volume of one IONP is V NP (4/ 3) × π × (d c /2) 3 (4/3) ×π× [(18 × 10 -7 cm)/2] 3 3,050 × 10 -21 cm 3 . The density of the IONP cores was assumed as the bulk density of Fe 3 O 4 which is 5.18 g/cm 3 (Kurzhals et al, 2017;Patsula et al, 2019). Therefore, the mass of each IONP is m NP ρ NP × V NP (5.18 g/cm 3 ) × (3,050 × 10 -21 cm 3 ) 15,800 × 10 -21 g. The number of IONPs (N NP ) in solution of volume V solution can be determined by dividing the total mass of dried IONPs (m NP,tot ) originating for a solution of V solution 1 ml by the mass of single nanoparticle N NP (m NP,tot /m NP ) (30 × 10 -3 g)/(15,800 × 10 -21 g) 0.0019×10 18 .…”

Recent Advances in Magnetite Nanoparticle Functionalization for Nanomedicine

“…The functionalization of magnetite nanoparticles with organic compounds is mostly done in order to improve their stability [192] and biocompatibility [193]. Another reason would be to improve their interaction with biological barriers (cellular membranes, vascular endothelium, blood-brain barrier) and facilitate the nanoparticles' passage through these [194,195].…”

Monodisperse Core-Shell NaYF4:Yb3+/Er3+@NaYF4:Nd3+-PEG-GGGRGDSGGGY-NH2 Nanoparticles Excitable at 808 and 980 nm: Design, Surface Engineering, and Application in Life Sciences

“…Such polymers include poly(acrylic acid), poly(ethylene glycol) (PEG) and its derivatives (e.g., PEG-neridronate), poly(vinylpyrrolidone), polyethyleneimine, poly(maleic anhydride-alt-1-octadecene), chitosan, dextran, etc. (Wilhelm et al, 2015;Gee and Xu, 2018;Mandl et al, 2019;Patsula et al, 2019).…”