Development and haematotoxicological evaluation of doped hydroxyapatite based multimodal nanocontrast agent for near-infrared, magnetic resonance and X-ray contrast imaging

Abstract

Multimodal molecular imaging provides both anatomical and molecular information, aiding early stage detection and better treatment planning of diseased conditions. Here, we report development and nanotoxicity evaluation of a novel hydroxyapatite nanoparticle (nHAp) based multimodal contrast agent for combined near-infrared (NIR), MR and X-ray imaging. Under optimised wet-chemical conditions, we achieved simultaneous doping of nHAp (size ∼50 nm) with indocyanine green and Gd³⁺ contributing to NIR contrast (∼750–850 nm), paramagnetic behaviour and X-ray absorption suitable for NIR, MR and X-ray contrast imaging, respectively. Haematocompatibility studies using stem cell viability, haemolysis, platelet activation, platelet aggregation and coagulation time analysis indicated excellent compatibility of doped nHAp (D-nHAp). Further, the immunogenic function studies using human lymphocytes (in vitro) showed that D-nHAp caused no adverse effects. Collectively, our studies suggest that D-nHAp with excellent biocompatibility and multifunctional properties is a promising nanocontrast agent for combined NIR, MR and X-ray imaging applications.

Keywords::

• Hydroxyapatite nanoparticles
• near-infrared imaging
• MRI
• X-ray contrast
• haematotoxicity

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Acknowledgement

We thank the Department of Biotechnology (DBT), Govt. of India for the financial support under the project “Nanotoxicology and Nanomedicine” (BT/PR9357/NNT/28/104/2007). We also thank the Department of Science and Technology (DST), Govt. of India for the financial support under “Nano-Theragnostics” (SR/NM/NS-99/2009). The authors also thank Dr. Rajesh Kannan, Dept. of Radiology, Amrita Institute of Medical Science, for MR measurements, Mr. Sajin P Ravi for his support in scanning electron microscopy and Mrs. Sreerekha PR for her valuable suggestions in haematotoxicity evaluation and FACS analysis.