Charge-Modulated Synthesis of Highly Stable Iron Oxide Nanoparticles for In Vitro and In Vivo Toxicity Evaluation

The surface charge of iron oxide nanoparticles (IONPs) plays a critical role in the interactions between nanoparticles and biological components, which significantly affects their toxicity in vitro and in vivo. In this study, we synthesized three differently charged IONPs (negative, neutral, and positive) based on catechol-derived dopamine, polyethylene glycol, carboxylic acid, and amine groups, via reversible addition–fragmentation chain transfer-mediated polymerization (RAFT polymerization) and ligand exchange. The zeta potentials of the negative, neutral, and positive IONPs were −39, −0.6, and +32 mV, respectively, and all three IONPs showed long-term colloidal stability for three months in an aqueous solution without agglomeration. The cytotoxicity of the IONPs was studied by analyzing cell viability and morphological alteration in three human cell lines, A549, Huh-7, and SH-SY5Y. Neither IONP caused significant cellular damage in any of the three cell lines. Furthermore, the IONPs showed no acute toxicity in BALB/c mice, in hematological and histological analyses. These results indicate that our charged IONPs, having high colloidal stability and biocompatibility, are viable for bio-applications.

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Biodistribution and Toxicity Assessment of Superparamagnetic Iron Oxide Nanoparticles In Vitro and In Vivo

Current Medical Science ◽

10.1007/s11596-018-1989-8 ◽

2018 ◽

Vol 38 (6) ◽

pp. 1096-1102 ◽

Cited By ~ 10

Author(s):

Qin Yu ◽

Xiao-qin Xiong ◽

Lei Zhao ◽

Ting-ting Xu ◽

Hao Bi ◽

...

Keyword(s):

Iron Oxide ◽

Iron Oxide Nanoparticles ◽

Superparamagnetic Iron Oxide ◽

Toxicity Assessment ◽

Superparamagnetic Iron Oxide Nanoparticles ◽

Oxide Nanoparticles

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LAPONITE®-stabilized iron oxide nanoparticles for in vivo MR imaging of tumors

Biomaterials Science ◽

10.1039/c5bm00508f ◽

2016 ◽

Vol 4 (3) ◽

pp. 474-482 ◽

Cited By ~ 24

Author(s):

Ling Ding ◽

Yong Hu ◽

Yu Luo ◽

Jianzhi Zhu ◽

Yilun Wu ◽

...

Keyword(s):

Iron Oxide ◽

Mr Imaging ◽

Iron Oxide Nanoparticles ◽

Colloidal Stability ◽

Coprecipitation Method ◽

Oxide Nanoparticles

LAPONITE®-stabilized iron oxide nanoparticles with great colloidal stability and high T2 relaxivity are synthesized by a facile controlled coprecipitation method, and can significantly enhance the contrast of tumors in vivo, indicating their tremendous potential in MR imaging applications.

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Efficient and Rapid Labeling of Transplanted Cell Populations with Superparamagnetic Iron Oxide Nanoparticles Using Cell Surface Chemical Biotinylation for in Vivo Monitoring by MRI

Cell Transplantation ◽

10.3727/096368910x498250 ◽

2010 ◽

Vol 19 (4) ◽

pp. 419-429 ◽

Cited By ~ 20

Author(s):

Po-Wah So ◽

Tammy Kalber ◽

David Hunt ◽

Michael Farquharson ◽

Alia Al-Ebraheem ◽

...

Keyword(s):

Iron Oxide ◽

Iron Oxide Nanoparticles ◽

Cell Tracking ◽

Superparamagnetic Iron Oxide ◽

Superparamagnetic Iron Oxide Nanoparticles ◽

Cell Populations ◽

Oxide Nanoparticles ◽

Signal Loss

Determination of the dynamics of specific cell populations in vivo is essential for the development of cell-based therapies. For cell tracking by magnetic resonance imaging (MRI), cells need to internalize, or be surface labeled with a MRI contrast agent, such as superparamagnetic iron oxide nanoparticles (SPIOs): SPIOs give rise to signal loss by gradient-echo and T2-weighted MRI techniques. In this study, cancer cells were chemically tagged with biotin and then magnetically labeled with anti-biotin SPIOs. No significant detrimental effects on cell viability or death were observed following cell biotinylation. SPIO-labeled cells exhibited signal loss compared to non-SPIO-labeled cells by MRI in vitro. Consistent with the in vitro MRI data, signal attenuation was observed in vivo from SPIO-labeled cells injected into the muscle of the hind legs, or implanted subcutaneously into the flanks of mice, correlating with iron detection by histochemical and X-ray fluorescence (XRF) methods. To further validate this approach, human mesenchymal stem cells (hMSCs) were also employed. Chemical biotinylation and SPIO labeling of hMSCs were confirmed by fluorescence microscopy and flow cytometry. The procedure did not affect proliferation and multipotentiality, or lead to increased cell death. The SPIO-labeled hMSCs were shown to exhibit MRI signal reduction in vitro and was detectable in an in vivo model. In this study, we demonstrate a rapid, robust, and generic methodology that may be a useful and practical adjuvant to existing methods of cell labeling for in vivo monitoring by MRI. Further, we have shown the first application of XRF to provide iron maps to validate MRI data in SPIO-labeled cell tracking studies.

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