Herein, we describe a novel approach for targeting of ubiquitous protein apoferritin (APO)-encapsulating doxorubicin (DOX) to prostate cancer using antibodies against prostate-specific membrane antigen (PSMA). The conjugation of anti-PSMA antibodies and APO was carried out using HWRGWVC heptapeptide, providing their site-directed orientation. The prostate-cancer-targeted and nontargeted nanocarriers were tested using LNCaP and HUVEC cell lines. A total of 90% of LNCaP cells died after treatment with DOX (0.25 μM) or DOX in nontargeted and prostate-cancer-targeted APO, proving that the encapsulated DOX toxicity for LNCaP cells remained the same. Free DOX showed higher toxicity for nonmalignant cells, whereas the toxicity was lower after treatment with the same dosage of APO-encapsulated DOX (APODOX) and even more in prostate-cancer-targeted APODOX. Hemolytic assay revealed exceptional hemocompatibility of the entire nanocarrier. The APO encapsulation mechanism ensures applicability using a wide variety of chemotherapeutic drugs, and the presented surface modification enables targeting to various tumors.

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Sapphires related to alkali basalts from the Cerová Highlands, Western Carpathians (southern Slovakia): composition and originBlue, grey-pink and pink sapphires from the Cerová Highlands, Western Carpathians (southern Slovakia) have been studied using CL, LA-ICP-MS, EMPA, and oxygen isotope methods. The sapphire occurs as (1) clastic heavy mineral in the secondary sandy filling of a Pliocene alkali basaltic maar at Hajnáčka, and (2) crystals in a pyroxenebearing syenite/anorthoclasite xenolith of Pleistocene alkali basalt near Gortva. Critical evaluation of compositional diagrams (Fe, Ti, Cr, Ga, Mg contents, Fe/Ti, Cr/Ga, Ga/Mg ratios) suggests a magmatic origin for clastic blue sapphires with lower Cr and Mg, but higher Fe and Ti concentrations in comparison to the grey-pink and pink varietes, as well as similar compositional trends with blue sapphire from the Gortva magmatic xenolith. Moreover, blue sapphires show similar δ18O values: 5.1 ‰ in the Gortva xenolith, 3.8 and 5.85 ‰ in the Hajnáčka placer, closely comparable to mantle to lower crustal magmatic rocks. On the contrary, pink and grey-pink sapphires show higher Cr and Mg, but lower Fe and Ti contents and their composition points to a metamorphic (metasomatic) origin.

Lead oxide nanoparticles (PbONPs), upon their entry into the lungs via inhalation, induce structural changes in primary and secondary target organs. The fate and ultrastructural localization of PbONPs in organs is known to be dependent on the specific organ. Here, we focused on the differences in the ability to clear the inhaled PbONPs from secondary target organs and on molecular and cellular mechanisms contributing to nanoparticle removal. Mice were exposed to PbONPs in whole-body inhalation chambers. Clearance of ionic lead and PbONPs (Pb/PbONPs) from the lungs and liver was very effective, with the lead being almost completely eliminated from the lungs and the physiological state of the lung tissue conspicuously restored. Kidneys exposed to nanoparticles did not exhibit serious signs of damage; however, LA-ICP-MS uncovered a certain amount of lead located preferentially in the kidney cortex even after a clearance period. The concentration of lead in femurs, as representatives of the axial skeleton, was the highest among studied organs at all designated time points after PbONP exposure, and the clearance ability of lead from the femurs was very low in contrast to other organs. The organ-specific increase of ABC transporters expression (ABCG2 in lungs and ABCC3 in the liver) was observed in exposed animals, suggesting their involvement in removing Pb/PbONPs from tissues. Moreover, the expression of caveolins and clathrin displayed a tissue-specific response to lead exposure. Our results uncovered high variability among the organs in their ability to clear Pb/PbONPs and in the transporters involved in this process.