Ad6-Based GM-CSF Expressing Vector Displays Oncolytic and Immunostimulatory Effects in an Immunocompetent Syrian Hamster Model of Cholangiocarcinoma.

Cholangiocarcinoma (CCA), the second most common liver cancer, remains highly resistant to chemotherapy and radiotherapy, leaving patients with unresectable tumors in urgent need of innovative therapeutic approaches. Adenovirus type 6 (Ad6), a species C human adenovirus, offers significant potential for cancer therapy due to its low seroprevalence compared to Adenovirus type 5 (Ad5) and its ability to evade Kupffer cells during systemic delivery. In this study, we developed a novel oncolytic adenovirus vector based on the Ad6 engineered to express human GM-CSF (Ad6-d24-GM) and evaluated its therapeutic efficacy in a novel immunocompetent, replication-permissive Syrian hamster model of CCA.

Cardioinotropic Effects in Subchronic Intoxication of Rats with Lead and/or Cadmium Oxide Nanoparticles.

Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections with lead oxide (PbO) and/or cadmium oxide (CdO) nanoparticles (NPs) 3 times a week during 6 weeks for the purpose of examining its effects on the contractile characteristics of isolated right ventricle trabeculae and papillary muscles in isometric and afterload contractions. Isolated and combined intoxication with these NPs was observed to reduce the mechanical work produced by both types of myocardial preparation. Using the in vitro motility assay, we showed that the sliding velocity of regulated thin filaments drops under both isolated and combined intoxication with CdO-NP and PbO-NP.

Comparative and Combined Vasotoxicity of Nanoparticles Containing Lead and Cadmium.

toxicological experiments were performed on an endothelial cell line exposed to different doses of spherical nanoparticles of cadmium and/or of lead sulfides with mean diameter 37 ± 5 nm and 24 ± 4 nm, respectively. Toxic effects were estimated by Luminescent Cell Viability Assay, endothelin-1 concentration and cell size determination. Some dose-response relationships were typically monotonic (well approximated with hyperbolic function) while others were bi- or even 3-phasic and could be described within the expanded hormesis paradigm.

Some data on the comparative and combined toxic activity of nanoparticles containing lead and cadmium with special attention to their vasotoxicity.

Moderate subchronic intoxication was induced in rats by repeated intraperitoneal injections of PbO (49.6 ± 16.0 nm) and/or CdO (57.

An overview of experiments with lead-containing nanoparticles performed by the Ekaterinburg nanotoxicological research team.

Over the past few years, the Ekaterinburg (Russia) interdisciplinary nanotoxicological research team has carried out a series of investigations using different and experimental models in order to elucidate the cytotoxicity and organ-systemic and organism-level toxicity of lead-containing nanoparticles (NP) acting separately or in combinations with some other metallic NPs. The authors claim that their many-sided experience in this field is unique and that some of their important results have been obtained for the first time. This paper is an overview of the team's previous publications in different journals.

Manifestation of Systemic Toxicity in Rats after a Short-Time Inhalation of Lead Oxide Nanoparticles.

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m during 5 days for 4 h a day in a nose-only setup.

Toxic Effects of Low-Level Long-Term Inhalation Exposures of Rats to Nickel Oxide Nanoparticles.

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m³ for 4 h a day 5 times a week for up to 10 months.

Combined Subchronic Toxicity of Aluminum (III), Titanium (IV) and Silicon (IV) Oxide Nanoparticles and Its Alleviation with a Complex of Bioprotectors.

Stable suspensions of metal/metalloid oxide nanoparticles (MeO-NPs) obtained by laser ablation of 99.99% pure elemental aluminum, titanium or silicon under a layer of deionized water were used separately, or in three binary combinations, or in a ternary combination to induce subchronic intoxications in rats. To this end, the MeO-NPs were repeatedly injected intraperitoneally (i.

Plasmonic photothermal therapy of atherosclerosis with nanoparticles: long-term outcomes and safety in NANOM-FIM trial.

Aim: The safety options in nanomedicine raise an issue of the optimal niche at the real-world clinical practice.

Methods: This is an observational prospective cohort analysis of the 5-year clinical outcomes at the intention-to-treat population (nano vs ferro vs stenting; n = 180) of NANOM first-in-man trial (NCT01270139).

Results: Mortality (6 vs 9 vs 10 cases of cardiac death in groups, p < 0.

A paradoxical response of the rat organism to long-term inhalation of silica-containing submicron (predominantly nanoscale) particles of a collected industrial aerosol at realistic exposure levels.

While engineered SiO nanoparticle toxicity is being widely investigated, mostly on cell lines or in acute animal experiments, the practical importance of as well as the theoretical interest in industrial condensation aerosols with a high SiO particle content seems to be neglected. That is why, to the best of our knowledge, long-term inhalation exposure to nano-SiO has not been undertaken in experimental nanotoxicology studies. To correct this data gap, female white rats were exposed for 3 or 6 months 5 times a week, 4h a day to an aerosol containing predominantly submicron (nanoscale included) particles of amorphous silica at an exposure concentration of 2.

In vivo toxicity of copper oxide, lead oxide and zinc oxide nanoparticles acting in different combinations and its attenuation with a complex of innocuous bio-protectors.

Stable suspensions of metal oxide nanoparticles (Me-NPs) obtained by laser ablation of 99.99% pure copper, zinc or lead under a layer of deionized water were used separately, in three binary combinations and a triple combination in two independent experiments on rats. In one of the experiments the rats were instilled with Me-NPs intratracheally (i.

Some patterns of metallic nanoparticles' combined subchronic toxicity as exemplified by a combination of nickel and manganese oxide nanoparticles.

Stable suspensions of NiO and/or Mn3O4 nanoparticles with a mean diameter of 16.7 ± 8.2 nm and 18.

Attenuation of Combined Nickel(II) Oxide and Manganese(II, III) Oxide Nanoparticles' Adverse Effects with a Complex of Bioprotectors.

Stable suspensions of NiO and Mn₃O₄ nanoparticles (NPs) with a mean (±s.d.) diameter of 16.

Some inferences from in vivo experiments with metal and metal oxide nanoparticles: the pulmonary phagocytosis response, subchronic systemic toxicity and genotoxicity, regulatory proposals, searching for bioprotectors (a self-overview).

The purpose of this paper is to overview and summarize previously published results of our experiments on white rats exposed to either a single intratracheal instillation or repeated intraperitoneal injections of silver, gold, iron oxide, copper oxide, nickel oxide, and manganese oxide nanoparticles (NPs) in stable water suspensions without any chemical additives. Based on these results and some corroborating data of other researchers we maintain that these NPs are much more noxious on both cellular and systemic levels as compared with their 1 μm or even submicron counterparts. However, within the nanometer range the dependence of systemic toxicity on particle size is intricate and non-unique due to complex and often contra-directional relationships between the intrinsic biological aggressiveness of the specific NPs, on the one hand, and complex mechanisms that control their biokinetics, on the other.

Some characteristics of free cell population in the airways of rats after intratracheal instillation of copper-containing nano-scale particles.

We used stable water suspensions of copper oxide particles with mean diameter 20 nm and of particles containing copper oxide and element copper with mean diameter 340 nm to assess the pulmonary phagocytosis response of rats to a single intratracheal instillation of these suspensions using optical, transmission electron, and semi-contact atomic force microscopy and biochemical indices measured in the bronchoalveolar lavage fluid. Although both nano and submicron ultrafine particles were adversely bioactive, the former were found to be more toxic for lungs as compared with the latter while evoking more pronounced defense recruitment of alveolar macrophages and especially of neutrophil leukocytes and more active phagocytosis. Based on our results and literature data, we consider both copper solubilization and direct contact with cellular organelles (mainly, mitochondria) of persistent particles internalized by phagocytes as probable mechanisms of their cytotoxicity.

Comparative in vivo assessment of some adverse bioeffects of equidimensional gold and silver nanoparticles and the attenuation of nanosilver's effects with a complex of innocuous bioprotectors.

Stable suspensions of nanogold (NG) and nanosilver (NS) with mean particle diameter 50 and 49 nm, respectively, were prepared by laser ablation of metals in water. To assess rat's pulmonary phagocytosis response to a single intratracheal instillation of these suspensions, we used optical, transmission electron, and semi-contact atomic force microscopy. NG and NS were also repeatedly injected intraperitoneally into rats at a dose of 10 mg/kg (0.