Veno Kononenko

Nanoparticle interaction with the immune system.

Abstract When nanoparticles enter the body, their interactions with cells are almost unavoidable. Unintended nanoparticle interaction with immune cells may elicit a molecular response that can have toxic effects and lead to greater susceptibility to infectious diseases, autoimmune disorders, and cancer development. As evidenced by several studies, nanoparticle interactions with biological systems can stimulate inflammatory or allergic reactions and activate the complement system. Nanoparticles can also stimulate immune response by acting as adjuvants or as haptens. Immunosuppressive effects have also been reported. This article gives a brief review of in vitro and in vivo research evidencing stimulatory or suppressive effects of nanoparticles on the immune system of mammals. In order to ensure safe use of nanosized particles, future research should focus on how their physical and chemical properties influence their behaviour in the biological environment, as they not only greatly affect nanoparticle-immune system interactions but can also interfere with experimental assays Ko nanodelci vstopijo v organizem, pridejo v kontakt s celicami imunskega sistema. Nezaželene interakcije nanodelcev z imunskim sistemom lahko sprožijo molekularni odziv, ki lahko pripelje do toksičnih učinkov in povečane dovzetnosti organizma za okužbe, avtoimunska obolenja ter razvoj raka. Dosedanje raziskave so pokazale, da nanodelci lahko sprožijo vnetne in alergijske reakcije, lahko pa tudi aktivirajo sistem komplementa. Nanodelci lahko delujejo kot adjuvansi ali kot hapteni. Obstajajo pa tudi poročila, ki kažejo na sposobnost nanodelcev, da zavrejo imunski odziv. V članku bomo povzeli ugotovitve dosedanjih raziskav in vitro ter in vivo, ki so bile narejene na področju proučevanja vplivov nanodelcev na stimulacijo ali supresijo imunskega sistema sesalcev. Za zagotovitev varne uporabe nanodelcev moramo razumeti kako fizikalno-kemijske lastnosti nanodelcev vplivajo na njihovo obnašanje v biološkem okolju. Lastnosti nanodelcev moramo upoštevati tudi ob izvajanju poskusov, da se izognemo lažnim rezultatom zaradi potencialne interference nanodelcev z dejavniki v eksperimentalnem okolju. Čeprav je bilo do sedaj narejenih že več nanotoksikoloških raziskav, je vpliv nanodelcev na imunski sistem še vedno slabo razumljen. Sposobnost nanodelcev za modulacijo imunskega odziva narekuje potrebo po nadaljnjih raziskavah interakcij nanodelcev z imunskim sistemom.

Multifunctional Gadolinium‐Doped Mesoporous TiO2 Nanobeads: Photoluminescence, Enhanced Spin Relaxation, and Reactive Oxygen Species Photogeneration, Beneficial for Cancer Diagnosis and Treatment

Materials with controllable multifunctional abilities for optical imaging (OI) and magnetic resonant imaging (MRI) that also can be used in photodynamic therapy are very interesting for future applications. Mesoporous TiO2 sub-micrometer particles are doped with gadolinium to improve photoluminescence functionality and spin relaxation for MRI, with the added benefit of enhanced generation of reactive oxygen species (ROS). The Gd-doped TiO2 exhibits red emission at 637 nm that is beneficial for OI and significantly improves MRI relaxation times, with a beneficial decrease in spin-lattice and spin-spin relaxation times. Density functional theory calculations show that Gd3+ ions introduce impurity energy levels inside the bandgap of anatase TiO2 , and also create dipoles that are beneficial for charge separation and decreased electron-hole recombination in the doped lattice. The Gd-doped TiO2 nanobeads (NBs) show enhanced ability for ROS monitored via • OH radical photogeneration, in comparison with undoped TiO2 nanobeads and TiO2 P25, for Gd-doping up to 10%. Cellular internalization and biocompatibility of TiO2 @xGd NBs are tested in vitro on MG-63 human osteosarcoma cells, showing full biocompatibility. After photoactivation of the particles, anticancer trace by means of ROS photogeneration is observed just after 3 min irradiation.

Comparative in vitro genotoxicity study of ZnO nanoparticles, ZnO macroparticles and ZnCl2 to MDCK kidney cells: Size matters.

In the present study, we evaluated the roles that ZnO particle size and Zn ion release have on cyto- and genotoxicity in vitro. The Madin-Darby canine kidney (MDCK) cells were treated with ZnO nanoparticles (NPs), ZnO macroparticles (MPs), and ZnCl2 as a source of free Zn ions. We first tested cytotoxicity to define sub-cytotoxic exposure concentrations and afterwards we performed alkaline comet and cytokinesis-block micronucleus assays. Additionally, the activities of both catalase (CAT) and glutathione S-transferase (GST) were evaluated in order to examine the potential impairment of cellular stress-defence capacity. The amount of dissolved Zn ions from ZnO NPs in the cell culture medium was evaluated by an optimized voltammetric method. The results showed that all the tested zinc compounds induced similar concentration-dependent cytotoxicity, but only ZnO NPs significantly elevated DNA and chromosomal damage, which was accompanied by a reduction of GST and CAT activity. Although Zn ion release from ZnO NPs in cell culture medium was significant, our results show that this reason alone cannot explain the ZnO genotoxicity seen in this experiment. We discuss that genotoxicity of ZnO NPs depends on the particle size, which determines the physical principles of their dissolution and cellular internalisation.

Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

Abstract The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro and in vivo studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO2-SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO2-SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO2-SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time- and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO2-SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account.

Effect of carbon black nanomaterial on biological membranes revealed by shape of human erythrocytes, platelets and phospholipid vesicles.

BackgroundWe studied the effect of carbon black (CB) agglomerated nanomaterial on biological membranes as revealed by shapes of human erythrocytes, platelets and giant phospholipid vesicles. Diluted human blood was incubated with CB nanomaterial and observed by different microscopic techniques. Giant unilamellar phospholipid vesicles (GUVs) created by electroformation were incubated with CB nanomaterial and observed by optical microscopy. Populations of erythrocytes and GUVs were analyzed: the effect of CB nanomaterial was assessed by the average number and distribution of erythrocyte shape types (discocytes, echinocytes, stomatocytes) and of vesicles in test suspensions, with respect to control suspensions. Ensembles of representative images were created and analyzed using computer aided image processing and statistical methods. In a population study, blood of 14 healthy human donors was incubated with CB nanomaterial. Blood cell parameters (concentration of different cell types, their volumes and distributions) were assessed.ResultsWe found that CB nanomaterial formed micrometer-sized agglomerates in citrated and phosphate buffered saline, in diluted blood and in blood plasma. These agglomerates interacted with erythrocyte membranes but did not affect erythrocyte shape locally or globally. CB nanomaterial agglomerates were found to mediate attractive interaction between blood cells and to present seeds for formation of agglomerate - blood cells complexes. Distortion of disc shape of resting platelets due to incubation with CB nanomaterial was not observed. CB nanomaterial induced bursting of GUVs while the shape of the remaining vesicles was on the average more elongated than in control suspension, indicating indirect osmotic effects of CB nanomaterial.ConclusionsCB nanomaterial interacts with membranes of blood cells but does not have a direct effect on local or global membrane shape in physiological in vitro conditions. Blood cells and GUVs are convenient and ethically acceptable methods for the study of effects of various substances on biological membranes and therefrom derived effects on organisms.

Nanoparticle interaction with the immune system / Interakcije nanodelcev z imunskim sistemom

Abstract When nanoparticles enter the body, their interactions with cells are almost unavoidable. Unintended nanoparticle interaction with immune cells may elicit a molecular response that can have toxic effects and lead to greater susceptibility to infectious diseases, autoimmune disorders, and cancer development. As evidenced by several studies, nanoparticle interactions with biological systems can stimulate inflammatory or allergic reactions and activate the complement system. Nanoparticles can also stimulate immune response by acting as adjuvants or as haptens. Immunosuppressive effects have also been reported. This article gives a brief review of in vitro and in vivo research evidencing stimulatory or suppressive effects of nanoparticles on the immune system of mammals. In order to ensure safe use of nanosized particles, future research should focus on how their physical and chemical properties influence their behaviour in the biological environment, as they not only greatly affect nanoparticle-immune system interactions but can also interfere with experimental assays Ko nanodelci vstopijo v organizem, pridejo v kontakt s celicami imunskega sistema. Nezaželene interakcije nanodelcev z imunskim sistemom lahko sprožijo molekularni odziv, ki lahko pripelje do toksičnih učinkov in povečane dovzetnosti organizma za okužbe, avtoimunska obolenja ter razvoj raka. Dosedanje raziskave so pokazale, da nanodelci lahko sprožijo vnetne in alergijske reakcije, lahko pa tudi aktivirajo sistem komplementa. Nanodelci lahko delujejo kot adjuvansi ali kot hapteni. Obstajajo pa tudi poročila, ki kažejo na sposobnost nanodelcev, da zavrejo imunski odziv. V članku bomo povzeli ugotovitve dosedanjih raziskav in vitro ter in vivo, ki so bile narejene na področju proučevanja vplivov nanodelcev na stimulacijo ali supresijo imunskega sistema sesalcev. Za zagotovitev varne uporabe nanodelcev moramo razumeti kako fizikalno-kemijske lastnosti nanodelcev vplivajo na njihovo obnašanje v biološkem okolju. Lastnosti nanodelcev moramo upoštevati tudi ob izvajanju poskusov, da se izognemo lažnim rezultatom zaradi potencialne interference nanodelcev z dejavniki v eksperimentalnem okolju. Čeprav je bilo do sedaj narejenih že več nanotoksikoloških raziskav, je vpliv nanodelcev na imunski sistem še vedno slabo razumljen. Sposobnost nanodelcev za modulacijo imunskega odziva narekuje potrebo po nadaljnjih raziskavah interakcij nanodelcev z imunskim sistemom.

Interakcije nanodelcev z imunskim sistemom

Abstract When nanoparticles enter the body, their interactions with cells are almost unavoidable. Unintended nanoparticle interaction with immune cells may elicit a molecular response that can have toxic effects and lead to greater susceptibility to infectious diseases, autoimmune disorders, and cancer development. As evidenced by several studies, nanoparticle interactions with biological systems can stimulate inflammatory or allergic reactions and activate the complement system. Nanoparticles can also stimulate immune response by acting as adjuvants or as haptens. Immunosuppressive effects have also been reported. This article gives a brief review of in vitro and in vivo research evidencing stimulatory or suppressive effects of nanoparticles on the immune system of mammals. In order to ensure safe use of nanosized particles, future research should focus on how their physical and chemical properties influence their behaviour in the biological environment, as they not only greatly affect nanoparticle-immune system interactions but can also interfere with experimental assays Ko nanodelci vstopijo v organizem, pridejo v kontakt s celicami imunskega sistema. Nezaželene interakcije nanodelcev z imunskim sistemom lahko sprožijo molekularni odziv, ki lahko pripelje do toksičnih učinkov in povečane dovzetnosti organizma za okužbe, avtoimunska obolenja ter razvoj raka. Dosedanje raziskave so pokazale, da nanodelci lahko sprožijo vnetne in alergijske reakcije, lahko pa tudi aktivirajo sistem komplementa. Nanodelci lahko delujejo kot adjuvansi ali kot hapteni. Obstajajo pa tudi poročila, ki kažejo na sposobnost nanodelcev, da zavrejo imunski odziv. V članku bomo povzeli ugotovitve dosedanjih raziskav in vitro ter in vivo, ki so bile narejene na področju proučevanja vplivov nanodelcev na stimulacijo ali supresijo imunskega sistema sesalcev. Za zagotovitev varne uporabe nanodelcev moramo razumeti kako fizikalno-kemijske lastnosti nanodelcev vplivajo na njihovo obnašanje v biološkem okolju. Lastnosti nanodelcev moramo upoštevati tudi ob izvajanju poskusov, da se izognemo lažnim rezultatom zaradi potencialne interference nanodelcev z dejavniki v eksperimentalnem okolju. Čeprav je bilo do sedaj narejenih že več nanotoksikoloških raziskav, je vpliv nanodelcev na imunski sistem še vedno slabo razumljen. Sposobnost nanodelcev za modulacijo imunskega odziva narekuje potrebo po nadaljnjih raziskavah interakcij nanodelcev z imunskim sistemom.