Synthesis, Characterization and In-Vitro Anti-Cancer Activity of Vanadium-Doped Nanocrystalline Hydroxyapatite
New Journal of Chemistry 2019
Daina Kalniņa, Aviva Levina, Alexander Pei, Kārlis-Agris Gross, Peter A. Lay

Vanadium drugs have been known for more than a century, but clinical translation has been hampered by unfavorable pharmacokinetics and lack of reliable delivery systems. Because of considerable interest in hydroxyapatite (HAP; Ca10(PO4)6(OH)2) nanoparticle-based drug delivery vehicles, particularly for the treatment of bone disease, and the wellknown chemical similarity between phosphate and vanadate, we report the first detailed studies of the reactivity under biologically relevant conditions, as well as the in vitro anti-cancer activity of vanadate-substituted HAP. Nanocrystalline vanadium-doped HAP (up to ~10% mol V relative to P) was prepared by partial substitution of phosphate with vanadate. This substitution does not significantly alter the HAP crystal lattice (X-ray powder diffraction), but surprisingly, the V(V) local structure is not tetrahedral. X-ray absorption spectroscopy showed that it has a [V(O)2(O’)2(OH)]4− coordination mode, with two short and two long V-O bonds from vanadate, and a weak interaction with an OH− ligand from the HAP structure. Also surprising is the partial reduction of V(V) to V(IV) within the crystal lattice of HAP under biomimetic conditions (5.0 mM ascorbate, pH 7.4, 24 h at 310 K, XANES and EPR spectroscopies). Both original and ascorbate-reduced V-doped HAPs are strongly cytotoxic to cultured human bone cancer cells (SW1353) when HAP nanoparticles are dispersed into cell culture medium. Partial reduction of V(V) to V(IV) within HAP decreased V leaching into cell culture medium but increased the cytotoxicity, which suggested that the activity is not just due to extracellular V release, but rather involves uptake of the nanoparticles. These preliminary results warrant further studies of V-doped HAP for bone cancer treatments.

Atslēgas vārdi
Chemistry, Catalysis, Materials, Biological and Medicinal Studies

Kalniņa, D., Levina, A., Pei, A., Gross, K., Lay, P. Synthesis, Characterization and In-Vitro Anti-Cancer Activity of Vanadium-Doped Nanocrystalline Hydroxyapatite. New Journal of Chemistry, 2019, Vol. 43, No. 45, 17891.-17901.lpp. ISSN 1144-0546. e-ISSN 1369-9261. Pieejams: doi:10.1039/C9NJ03406D

Publikācijas valoda
English (en)
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