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Mesoporous multi-layered silica-coated luminescent Y 2 O 3 :Eu nanoparticles (NPs) were prepared by a urea-based decomposition process, and their surfaces were gradually modified with nanoporous and mesoporous silica layers using modified sol-gel methods. The synthesized luminescent core-shell NPs were characterized thoroughly to investigate their structural, morphological, thermal, optical, photo luminescent properties and their surface chemistry. The morphology of the core NPs were nearly spherical in shape and were nano-sized grains. The observed luminescent efficiency of the mesoporous multi-layered silica-coated luminescent core NPs was gradually reduced because of bond formation between the Y 2 O 3 :Eu core and the amorphous silica shell via YOSiOH bridges on the surface of the NPs; the bonds suppressed the non-radiative transition pathways. Biocompatibility tests on Human breast cancer cells using the 3‑(4,5‑Dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and lactate dehydrogenase assays indicated that the core-shell NPs were non-toxic even at high concentrations. The mesoporous SiO 2 layer played a key role in perfecting the solubility, biocompatibility, and non-toxicity of the NPs. The zeta potential, surface chemistry (Fourier transform infrared spectroscopy), and optical absorption spectral analyses revealed the high hydrophilicity of the as-prepared core-shell NPs because of the active surface-functionalized silanol (SiOH) groups, which could potentially offer many exciting opportunities in photonic-based biomedical applications., (Copyright © 2018 Elsevier B.V. All rights reserved.)