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Fluorescein-labeled fluoroapatite nanocrystals codoped with Yb(III) and Ho(III) for trimodal (downconversion, upconversion and magnetic resonance) imaging of cancer cells

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Abstract

The authors report on upconversion nanocrystals (NCs) based on a fluoroapatite (FAp) support that was engineered to enable multimodal imaging by fluorescence imaging (FI), magnetic resonance imaging (MRI), and upconversion luminescence imaging. A fluorescein based fluorophore (FITC) was incorporated into the FAp nanocrystals and then doped with Yb(III) and Ho(III) by microwave-assisted solution combustion synthesis. The hexagonal phase nanocrystals (FITC-FAp:Yb/Ho) exhibit spindle like morphology with an average diameter and length of 15 nm and 196 nm, respectively. The doping concentration of the Yb (5 %) and Ho (0.6 %) was determined by ICP-MS. The nanocrystals exhibit upconversion luminescence when irradiated with NIR light of wavelength 980 nm. The emission spectrum consists of two bands centered at 542 nm (green emission) and 654 nm (red emission) corresponding to two transitions of Ho(III). The pump power dependence of upconversion luminescence intensity confirmed the 2-photon process. The presence of FITC in the nanocrystal imparts green fluorescence (peaking at 521 nm) by a conventional downconversion process. The presence of Ho(III) endows the NCs with paramagnetism. The magnetization is 21.063 emu∙g−1 at room temperature. The NCs exhibit a longitudinal relaxivity (r1) of 0.12 s−1∙mM−1, and a transverse relaxivity (r2) of 29 s−1∙mM−1, which makes the system suitable for developing T2 MRI contrast agents. The nanocrystals are surface aminized using polyethyleneimine (PEI) and covalently conjugated to folic acid (FA) in order to target the folate receptors that are overexpressed in many cancer cells. The FA-conjugated nanocrystals have been tested for their applicability in fluorescence imaging of HeLa cells. Their biocompatibility, upconversion and downconversion luminescence, and magnetism render these NCs potentially powerful nanoprobes for trimodal imaging.

Fluorescein-labeled fluorapatite nanocrystals codoped with Yb(III) and Ho(III) ions (FITC-FAp:Yb/Ho) have been prepared through microwave route. The up and downconversion luminescence, biocompatibility and magnetism are explored. The folic acid conjugated nanocrystals are promising candidates for trimodal imaging (up- and downconversion imaging and magnetic resonance imaging)

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Acknowledgments

The authors thank Director, National Centre for Ultrafast Process (NCUP, University of Madras), Director, CSIR-NIIST (Thiruvananthapuram), Head, SAIF-IIT Madras, Director, IISER (Thiruvanathapuram), Director, SAIF-STIC-CUSAT (Kochi) and the Head, Department of Chemistry, University of Kerala (Kariavattom Campus), Thiruvananthapuram, for the sophisticated characterization techniques provided for the work. S.S. S would like to acknowledge University Grant Commission (UGC) New Delhi, for providing financial assistance through Teacher Fellowship under Faculty Improvement programme (FIP).

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  1. Department of Chemistry, University of Kerala, Kariavattom Campus, Trivandrum, Kerala, 695 581, India

    Sasidharanpillai S. Syamchand & George Sony

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  1. Sasidharanpillai S. Syamchand
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  2. George Sony
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Correspondence to George Sony.

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Syamchand, S.S., Sony, G. Fluorescein-labeled fluoroapatite nanocrystals codoped with Yb(III) and Ho(III) for trimodal (downconversion, upconversion and magnetic resonance) imaging of cancer cells. Microchim Acta 183, 3209–3219 (2016). https://doi.org/10.1007/s00604-016-1970-9

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