Silica Nanoparticles Provoke Cell Death Independent of p53 and BAX in Human Colon Cancer Cells

Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (–NH2 and –COOH). Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the silica NPs promoted apoptosis and necrosis proportional to the administered specific surface area dose. Cytotoxicity of silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of caspases partially prevented silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug cisplatin, silica NPs induced cell death independent of the p53–BAX axis. In conclusion, silica NPs initiated cell death in colon cancer cells dependent on the specific surface area and presence of serum. Further studies in vivo are warranted to address potential cytotoxic actions in the gut epithelium. The unintended toxicity of silica NPs as observed here could also be beneficial. As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells

Methods of Product Development and Problem Solving - An Approach to connecting Perspectives in Didactics of Technology

Für die Umsetzung von Unterricht im Fach Naturwissenschaft und Technik unter Berücksichtigung verschiedener technikdidaktischer Perspektiven fehlt es an übertragbaren Lehr-/Lernkonzepten. Mit Methoden der Produktentwicklung und Problemlösung wurde ein Ansatz entwickelt, um diese Herausforderung zu adressieren. Dazu wurden drei Schritte unternommen: (1) in einer Pilotstudie wurde die prinzipielle Machbarkeit untersucht. (2) Anschließend wurden innerhalb einer Lehrkräftefortbildung weitere Methoden ausgewählt und diese (3) in Lehreinheiten an Karlsruher Gymnasien erprobt und evaluiert. Die Einzelmaßnahmen wurden in Bezug auf Anwendbarkeit und Nutzen mittels strukturierter Fragebögen und Freitextfragen evaluiert. Die Ergebnisse zeigen einen subjektiven Mehrwert aus Sicht der Schüler/-innen.Sustainable teaching/learning concepts are required for the implementation of technology teaching in the subject science and technology, taking into account different perspectives. With methods of product development and problem solving, an approach has been developed to address this challenge. Three steps were taken to test this approach: (1) A pilot study was conducted to examine the principle feasibility. (2) Suitable methods were selected within an in-service teacher training course and these (3) were tested and evaluated in teaching units at Karlsruhe secondary schools. The individual measures were evaluated in terms of applicability and usefulness using structured questionnaires and free-text questions. The results show a subjective added value from the pupils' perspective

Silica Nanoparticles Provoke Cell Death Independent of p53 and BAX in Human Colon Cancer Cells

Several in vitro studies have suggested that silica nanoparticles (NPs) might induce adverse effects in gut cells. Here, we used the human colon cancer epithelial cell line HCT116 to study the potential cytotoxic effects of ingested silica NPs in the presence or absence of serum. Furthermore, we evaluated different physico-chemical parameters important for the assessment of nanoparticle safety, including primary particle size (12, 70, 200, and 500 nm) and surface modification (–NH2 and –COOH). Silica NPs triggered cytotoxicity, as evidenced by reduced metabolism and enhanced membrane leakage. Automated microscopy revealed that the silica NPs promoted apoptosis and necrosis proportional to the administered specific surface area dose. Cytotoxicity of silica NPs was suppressed by increasing amount of serum and surface modification. Furthermore, inhibition of caspases partially prevented silica NP-induced cytotoxicity. In order to investigate the role of specific cell death pathways in more detail, we used isogenic derivatives of HCT116 cells which lack the pro-apoptotic proteins p53 or BAX. In contrast to the anticancer drug cisplatin, silica NPs induced cell death independent of the p53–BAX axis. In conclusion, silica NPs initiated cell death in colon cancer cells dependent on the specific surface area and presence of serum. Further studies in vivo are warranted to address potential cytotoxic actions in the gut epithelium. The unintended toxicity of silica NPs as observed here could also be beneficial. As loss of p53 in colon cancer cells contributes to resistance against anticancer drugs, and thus to reoccurrence of colon cancer, targeted delivery of silica NPs could be envisioned to also deplete p53 deficient tumor cells

Microscopy-based high-throughput assays enable multi-parametric analysis to assess adverse effects of nanomaterials in various cell lines

Manufactured nanomaterials (MNMs) selected from a library of over 120 different MNMs with varied compositions, sizes, and surface coatings were tested by four different laboratories for toxicity by high-throughput/-content (HT/C) techniques. The selected particles comprise 14 MNMs composed of CeO2, Ag, TiO2, ZnO and SiO2 with different coatings and surface characteristics at varying concentrations. The MNMs were tested in different mammalian cell lines at concentrations between 0.5 and 250 µg/mL to link physical-chemical properties to multiple adverse effects. The cell lines are derived from relevant organs such as liver, lung, colon and the immune system. Endpoints such as viable cell count, cell membrane permeability, apoptotic cell death, mitochondrial membrane potential, lysosomal acidification and steatosis have been studied. Soluble MNMs, Ag and ZnO, were the most toxic in all cell types. TiO2 and SiO2 MNMs also triggered toxicity in some, but not all, cell types and the cell-type specific effects were influenced by the specific coating. CeO2 MNMs were nearly ineffective in our test systems. Differentiated liver cells appear to be most sensitive to MNMs, in particular to TiO2 MNMs. Whereas most of the investigated MNMs showed no acute toxicity, it became clear that some show adverse effects dependent on the assay and cell line. Hence, it is advised that future nanosafety studies utilise a multi-parametric approach such as HT/C screening to avoid missing signs of toxicity. Furthermore, some of the cell type specific effects should be followed up in more detail and might also provide an incentive to address potential adverse effects in vivo in the relevant organ.JRC.F.3-Chemicals Safety and Alternative Method