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Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.

ABSTRACT: Background: Submicron particles (SMPs), as novel bionanomaterials, offer complementary benefits to their conventional nano-counterparts. Aim: To explore zinc oxide (ZnO) SMPs' bioimaging and anticancer potentials. Materials & methods: ZnO SMPs were synthesized into two shapes. Fluorescent spectrum and microscopy were studied for the bioimaging property. Wound healing and Live/Dead assays of glioblastoma cells were characterized for anticancer activities. Results: ZnO SMPs exhibited a high quantum yield (49%) with stable orange fluorescence emission. Both morphologies (most significant in the rod shape) showed tumor-selective properties in cytotoxicity, inhibition to cell migration and attenuating the cancer-upregulated genes. The tumor selectivity was attributed to particle degradation and surface properties on pH dependency. Conclusion: The authors propose that ZnO SMPs could be a promising anticancer drug with tunable, morphology-dependent properties for bioimaging and controlled release.

SUBMITTER: Geng J

PROVIDER: S-EPMC9118057 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.

Geng Junnan J Jensen Gregory G Jackson Kyle K Pontsler Jefferson J Rengarajan Venkatakrishnan V Sun Yan Y Britt David D Huang Yu Y

Nanomedicine (London, England) 20220330 9

Background: Submicron particles (SMPs), as novel bionanomaterials, offer complementary benefits to their conventional nano-counterparts. Aim: To explore zinc oxide (ZnO) SMPs' bioimaging and anticancer potentials. Materials & methods: ZnO SMPs were synthesized into two shapes. Fluorescent spectrum and microscopy were studied for the bioimaging property. Wound healing and Live/Dead assays of glioblastoma cells were characterized for anticancer activities. Results: ZnO ...[more]

PMID: 35350869

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Project description:Inhalation of ZnO particles can cause inflammation of the airways and metal fume fever. It is unclear if different sizes of the particles alter these effects. However, various studies report higher biological activity of other nano-sized particles compared to microparticles. No effects at all were observed after inhalation of micro- and nano-sized zinc oxide (ZnO) particle concentrations of 0.5 mg/m3. Studies with different particle sizes of ZnO at higher exposures are not available. Accordingly, we hypothesized that inhalation of nano-sized ZnO particles induces stronger health effects than the inhalation of the same airborne mass concentration of micro-sized ZnO particles. 16 healthy volunteers (eight men, eight women) were exposed to filtered air and ZnO particles (2.0 mg/m3) for 2 h (one session with nano- and one with micro-sized ZnO) including 1 h of cycling at moderate workload. Effect parameters were symptoms, body temperature, inflammatory markers in blood and in induced sputum. Induced sputum was obtained at baseline examination, 22 h after exposure and at the end of the final test. The effects were assessed before, immediately after, about 22 h after, as well as two and three days after each exposure. Neutrophils, monocytes and acute-phase proteins in blood increased 22 h after micro- and nano-sized ZnO exposure. Effects were generally stronger with micro-sized ZnO particles. Parameters in induced sputum showed partial increases on the next day, but the effect strengths were not clearly attributable to particle sizes. The hypothesis that nano-sized ZnO particles induce stronger health effects than micro-sized ZnO particles was not supported by our data. The stronger systemic inflammatory responses after inhalation of micro-sized ZnO particles can be explained by the higher deposition efficiency of micro-sized ZnO particles in the respiratory tract and a substance-specific mode of action, most likely caused by the formation of zinc ions.

Project description:BACKGROUND: Predominantly, studies of nanoparticle (NPs) toxicology in vitro are based upon the exposure of submerged cell cultures to particle suspensions. Such an approach however, does not reflect particle inhalation. As a more realistic simulation of such a scenario, efforts were made towards direct delivery of aerosols to air-liquid-interface cultivated cell cultures by the use of aerosol exposure systems.This study aims to provide a direct comparison of the effects of zinc oxide (ZnO) NPs when delivered as either an aerosol, or in suspension to a triple cell co-culture model of the epithelial airway barrier. To ensure dose-equivalence, ZnO-deposition was determined in each exposure scenario by atomic absorption spectroscopy. Biological endpoints being investigated after 4 or 24h incubation include cytotoxicity, total reduced glutathione, induction of antioxidative genes such as heme-oxygenase 1 (HO-1) as well as the release of the (pro)-inflammatory cytokine TNF?. RESULTS: Off-gases released as by-product of flame ZnO synthesis caused a significant decrease of total reduced GSH and induced further the release of the cytokine TNF?, demonstrating the influence of the gas phase on aerosol toxicology. No direct effects could be attributed to ZnO particles. By performing suspension exposure to avoid the factor "flame-gases", particle specific effects become apparent. Other parameters such as LDH and HO-1 were not influenced by gaseous compounds: Following aerosol exposure, LDH levels appeared elevated at both timepoints and the HO-1 transcript correlated positively with deposited ZnO-dose. Under submerged conditions, the HO-1 induction scheme deviated for 4 and 24h and increased extracellular LDH was found following 24h exposure. CONCLUSION: In the current study, aerosol and suspension-exposure has been compared by exposing cell cultures to equivalent amounts of ZnO. Both exposure strategies differ fundamentally in their dose-response pattern. Additional differences can be found for the factor time: In the aerosol scenario, parameters tend to their maximum already after 4h of exposure, whereas under submerged conditions, effects appear most pronounced mainly after 24h. Aerosol exposure provides information about the synergistic interplay of gaseous and particulate phase of an aerosol in the context of inhalation toxicology. Exposure to suspensions represents a valuable complementary method and allows investigations on particle-associated toxicity by excluding all gas-derived effects.

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Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.

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Versatile activity and morphological effects of zinc oxide submicron particles as anticancer agents.

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