ABSTRACT
In this work we adapt rare-earth-ion-doped NaYF4nanoparticles coated with a silicon oxide shell (NaYF4:20%Yb,0.2%Tm@SiO2) for biological and medical applications (for example, imaging of cancer cells and therapy at the nano level). The wide upconversion emission range under 980 nm excitation allows one to use the nanoparticles for cancer cell (4T1) photodynamic therapy (PDT) without a photosensitizer. The reactive oxygen species (ROS) are generated by Tm/Yb ion upconversion emission (blue and UV light). Thein vitroPDT was tested on 4T1 cells incubated with NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and irradiated with NIR light. After 24 h, cell viability decreased to below 10%, demonstrating very good treatment efficiency. High modification susceptibility of the SiO2shell allows for attachment of biological molecules (specific antibodies). In this work we attached the anti-human IgG antibody to silane-PEG-NHS-modified NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and a specifically marked membrane model by bio-conjugation. Thus, it was possible to perform a selective search (a high-quality optical method with a very low-level organic background) and eventually damage the targeted cancer cells. The study focuses on therapeutic properties of NaYF4:20%Yb,0.2%Tm@SiO2nanoparticles and demonstrates, upon biological functionalization, their potential for targeted therapy.
Subject(s)
Nanoparticles , Neoplasms , Photochemotherapy , Photosensitizing Agents , Reactive Oxygen Species/metabolism , Animals , Cell Line, Tumor , Female , Mice , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Neoplasms/drug therapy , Neoplasms/metabolism , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacokinetics , Photosensitizing Agents/pharmacology , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Silicon Dioxide/pharmacology , Thulium/chemistry , Thulium/pharmacokinetics , Thulium/pharmacology , Ytterbium/chemistry , Ytterbium/pharmacokinetics , Ytterbium/pharmacology , Yttrium/chemistry , Yttrium/pharmacokinetics , Yttrium/pharmacologyABSTRACT
Water-soluble upconversion nanoparticles (UCNPs), based on polyvinylpyrrolidone (PVP)-coated NaYF4:Er3+,Yb3+,Gd3+, with various concentrations of Gd3+ ions and relatively high upconversion efficiencies, were synthesized. The internalization and cytotoxicity of the thus obtained UCNPs were evaluated in three cell lines (HeLa, HEK293 and astrocytes). No cytotoxicity was observed even at concentrations of UCNPs up to 50 µg ml-1. The fate of the UCNPs within the cells was studied by examining their upconversion emission spectra with confocal microscopy and confirming these observations with transmission electron microscopy. It was found that the cellular uptake of the UCNPs occurred primarily by clathrin-mediated endocytosis, whereas they were secreted from the cells via lysosomal exocytosis. The results of this study, focused on the mechanisms of the cellular uptake, localization and secretion of UCNPs, demonstrate, for the first time, the co-localization of UCNPs within discrete cell organelles.
