Long-term biodistribution in vivo and toxicity of radioactive/magnetic hydroxyapatite nanorods.
Although nanoscale hydroxyapatite [Ca10(PO4)6(OH)2; HA] has been widely investigated as a carrier in the delivery of drugs, genes, or siRNA, the in vivo toxicity of nanoscale HA is not clear and the long-term dynamic distribution in vivo has not hitherto been visualized. In this work, gadolinium-doped HA nanorods (HA:Gd) with an r1 value of 5.49 s(-1) (mm)(-1) have been prepared by a hydrothermal method. Samarium-153 ((153)Sm) was then effectively post-labeled onto the HA:Gd ((153)Sm-HA:Gd) with a labeling rate of ∼100% and a radio-labeling stability in vitro of ∼100% over 48 h. The product could serve as a new dual-modality probe for SPECT and MR imaging in vivo. By means of SPECT and MRI, the HA:Gd nanorods were found to be quickly taken up by the mononuclear phagocyte system, especially the liver and spleen. The nanorods in the liver and lung tended to be eliminated within 24 h, but nanorods in the spleen behaved differently and proved difficult to excrete. In vitro studies by cell transmission electron microscopy (TEM) and methyl thiazolyl tetrazolium (MTT) assay showed good biocompatibility of the HA:Gd nanorods with HeLa cells, even at a high concentration. The indicators of body weight, histology, and serology demonstrated that the HA:Gd nanorods exhibited excellent biocompatibility in vivo for at least 61 days. Therefore, (153)Sm-HA:Gd nanorods with excellent relaxivity, γ-emission, and biosafety offer clear advantages and potential for bioapplications.
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China.
Ying
Y
Liu
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China; Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, China.
Yun
Y
Sun
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China.
Cong
C
Cao
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China.
Yang
Y
Yang
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China.
Yongquan
Y
Wu
Department of Biosynthesis, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: dianwenju@fudan.edu.cn.
Dianwen
D
Ju
Department of Chemistry, The State Key Laboratory of Molecular Engineering of Polymers, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address: fyli@fudan.edu.cn.
Fuyou
F
Li
D000818:Animals; D017886:Durapatite / Q000493:pharmacokinetics* / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D051379:Mice; D046529:Microscopy, Electron, Transmission; D043942:Nanotubes; D011868:Radioisotopes; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D011868:Radioisotopes; D017886:Durapatite
Biodistribution; Biosafety; Hydroxyapatite nanorods; Magnetic resonance imaging (MRI); Single photon emission computed tomography (SPECT)