Preclinical Study of Biofunctional Polymer-Coated Upconversion Nanoparticles.

Upconversion nanoparticles (UCNPs) are new-generation photoluminescent nanomaterials gaining considerable recognition in the life sciences due to their unique optical properties that allow high-contrast imaging in cells and tissues. Upconversion nanoparticle applications in optical diagnosis, bioassays, therapeutics, photodynamic therapy, drug delivery, and light-controlled release of drugs are promising, demanding a comprehensive systematic study of their pharmacological properties. We report on production of biofunctional UCNP-based nanocomplexes suitable for optical microscopy and imaging of HER2-positive cells and tumors, as well as on the comprehensive evaluation of their pharmacokinetics, pharmacodynamics, and toxicological properties using cells and laboratory animals. The nanocomplexes represent a UCNP core/shell structure of the NaYF4:Yb, Er, Tm/NaYF4 composition coated with an amphiphilic alternating copolymer of maleic anhydride with 1-octadecene (PMAO) and conjugated to the Designed Ankyrin Repeat Protein (DARPin 9_29) with high affinity to the HER2 receptor. We demonstrated the specific binding of UCNP-PMAO-DARPin to HER2-positive cancer cells in cultures and xenograft animal models allowing the tumor visualization for at least 24 h. An exhaustive study of the general and specific toxicity of UCNP-PMAO-DARPin including the evaluation of their allergenic, immunotoxic, and reprotoxic properties was carried out. The obtained experimental body of evidence leads to a conclusion that UCNP-PMAO and UCNP-PMAO-DARPin are functional, noncytotoxic, biocompatible, and safe for imaging applications in cells, small animals, and prospective clinical applications of image-guided surgery.

The Aral Sea disaster--human biomonitoring of Hg, As, HCB, DDE, and PCBs in children living in Aralsk-and Akchi, Kazakhstan.

Mercury and arsenic have been measured in urine samples and HCB, DDE and PCBs in blood samples of children from Aralsk and Akchi, Kazakhstan. Due to the special situation of Aralsk in the desert left by the drying out Aral Sea, environmental pollution with heavy metals and organic contaminants is believed to be higher than elsewhere in Kazakhstan. Aralsk was formerly located at the shore of the Aral Sea and is now far away from it. Akchi is a similar village and was included in this study as a Kazakh reference site. Urine concentrations of arsenic were higher in Akchi (9.4 microg/l) than in Aralsk (5.5 microg/l) and compared to children from Mannheim, Germany (4.25 microg/l; Median values). Regarding Hg, differences between children of Aralsk and Akchi were not significant and concentrations were lower than reference values from Germany. DDE contamination of children from Aralsk (2.48 microg/l) was significantly higher compared to Akchi (1.35 microg/l). DDE concentrations in blood samples from children in both cities were also significantly higher than the German reference value (0.7 microg/l). HCB and PCBs levels differed significantly between both Kazakh groups. However, concentrations of these compounds were lower than German reference values and there was no significant difference to samples from Mannheim children.