Pancreatic cancer is one of the most common forms of malignant disease with a poor survival prognosis. Currently, nanomedicine holds great promise for targeted diagnosis and treatment of this cancer, which also reduces toxic side effects. In this work, we prepared PEG-coated monodisperse upconversion nanoparticles (UCNPs) with a conjugated Flamma® fluorescent dye for imaging and detection of particle distribution in vivo. We performed a thorough physicochemical characterization of the particles and determined their colloidal and chemical stability in several aqueous media such as water, PBS, Dulbecco's modified Eagle's medium and artificial lysosomal fluid. Luminescence resonance energy transfer from the emission of UCNPs as a donor to the Flamma® as an acceptor was confirmed. Intraperitoneal versus intravenous administration was then compared in terms of biodistribution of particles in various organs in the orthotopic mice pancreatic cancer model. The intraperitoneal route was preferred over the intravenous one, because it significantly increased the accumulation of particles in the tumor tissue. These new UCNP@Ale-PEG-Flamma® nanoparticles are thus promising for new treatment avenues for pancreatic cancer.

• Publikační typ
• časopisecké články MeSH

In this study, spherical or hexagonal NaYF4:Yb,Er nanoparticles (UCNPs) with sizes of 25 nm (S-UCNPs) and 120 nm (L-UCNPs) were synthesized by high-temperature coprecipitation and subsequently modified with three kinds of polymers. These included poly(ethylene glycol) (PEG) and poly(N,N-dimethylacrylamide-co-2-aminoethylacrylamide) [P(DMA-AEA)] terminated with an alendronate anchoring group, and poly(methyl vinyl ether-co-maleic acid) (PMVEMA). The internalization of nanoparticles by rat mesenchymal stem cells (rMSCs) and C6 cancer cells (rat glial tumor cell line) was visualized by electron microscopy and the cytotoxicity of the UCNPs and their leaches was measured by the real-time proliferation assay. The comet assay was used to determine the oxidative damage of the UCNPs. An in vivo study on mice determined the elimination route and potential accumulation of UCNPs in the body. The results showed that the L- and S-UCNPs were internalized into cells in the lumen of endosomes. The proliferation assay revealed that the L-UCNPs were less toxic than S-UCNPs. The viability of rMSCs incubated with particles decreased in the order S-UCNP@Ale-(PDMA-AEA) > S-UCNP@Ale-PEG > S-UCNPs > S-UCNP@PMVEMA. Similar results were obtained in C6 cells. The oxidative damage measured by the comet assay showed that neat L-UCNPs caused more oxidative damage to rMSCs than all coated UCNPs while no difference was observed in C6 cells. An in vivo study indicated that L-UCNPs were eliminated from the body via the hepatobiliary route; L-UCNP@Ale-PEG particles were almost eliminated from the liver 96 h after intravenous application. Pilot fluorescence imaging confirmed the limited in vivo detection capabilities of the nanoparticles.

• Klíčová slova
• biological applications, toxicity, upconverting nanoparticles,
• MeSH
• krysa rodu Rattus MeSH
• mezenchymální kmenové buňky * metabolismus   účinky léků   cytologie   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nanočástice chemie   MeSH
• oxidační stres účinky léků   MeSH
• polyethylenglykoly chemie   MeSH
• velikost částic MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• polyethylenglykoly MeSH