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Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging
Published on: December 4, 2016
A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent
Anusha Ashokan1, Deepthy Menon, Shantikumar Nair
1Amrita Center for Nanosciences and Molecular Medicine, Amrita Institute of Medical Science & Research Center Campus, Amrita Vishwa Vidyapeetham University, Cochin, Kerala 682041, India.
Researchers developed a novel multi-modal contrast agent using hydroxyapatite nanocrystals (nHAp) for advanced medical imaging. This biocompatible agent enhances magnetic resonance imaging (MRI), X-ray, and near-infrared fluorescence imaging, showing promise for targeted cancer diagnosis.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Molecular Imaging
Background:
- Multi-modal molecular imaging enhances non-invasive diagnosis by integrating anatomical and disease-specific phenotypic information.
- Development of multifunctional contrast agents with sensing capabilities and high biocompatibility is crucial for combinatorial molecular imaging.
Purpose of the Study:
- To engineer a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp) for simultaneous MRI, X-ray, and near-infrared (NIR) fluorescence imaging.
- To functionalize the nHAp agent for targeted delivery to cancer cells expressing folate receptors.
- To evaluate the biocompatibility and safety of the developed contrast agent.
Main Methods:
- Synthesized monodispersed hydroxyapatite nanocrystals (nHAp) doped with rare-earth impurities (Eu3+ and Gd3+) using a wet-chemical method.
- Functionalized nHAp with polyethyleneimine (PEI) and folic acid (FA) to create FA-PEI-MF-nHAp conjugates for targeted cancer cell imaging.
- Assessed imaging capabilities (MRI, X-ray, NIR fluorescence), cellular targeting specificity, and nanotoxicity on various cell lines (HUVEC, L929, KB, A549).
Main Results:
- The engineered nHAp exhibited simultaneous contrast enhancement for MRI (r1 relaxivity ~12 mM−1 s−1), X-ray (~80% attenuation), and NIR fluorescence (700 nm).
- FA-PEI-MF-nHAp conjugates demonstrated specific targeting and aggregation on folate receptor-positive (FR+) cancer cells.
- Nanotoxicity studies showed no significant toxicity or reactive oxygen species (ROS) generation in treated cells, even at high concentrations.
Conclusions:
- The developed multifunctional nHAp (MF-nHAp) serves as a promising tri-modal contrast agent for combinatorial molecular imaging.
- Its ability to target specific molecular receptors and its biocompatibility make it suitable for advanced cancer diagnostics.
- This biomineral contrast agent offers a novel platform for enhanced non-invasive disease characterization.
