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

被引:77
|
作者
Patsula, Vitalii [1 ]
Horak, Daniel [1 ]
Kucka, Jan [1 ]
Mackova, Hana [1 ]
Lobaz, Volodymyr [1 ]
Francova, Pavla [2 ]
Herynek, Vit [2 ]
Heizer, Tomas [2 ]
Paral, Petr [2 ]
Sefc, Ludek [2 ]
机构
[1] Czech Acad Sci, Inst Macromol Chem, Heyrovskeho Nam 2, Prague 16206 6, Czech Republic
[2] Charles Univ Prague, Fac Med 1, Ctr Adv Preclin Imaging, Salmovska 3, Prague 12000 2, Czech Republic
关键词
IRON-OXIDE NANOPARTICLES; POLYETHYLENE-GLYCOL PEG; SURFACE FUNCTIONALIZATION; CONTRAST AGENTS; DRUG-DELIVERY; CHAIN-LENGTH; PEGYLATION; CLEARANCE; TOXICITY; POLYMER;
D O I
10.1038/s41598-019-47262-w
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Magnetite (Fe3O4) 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 degrees 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 Fe3O4 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.
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页数:12
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