High-throughput synthesis of CeO2 nanoparticles for transparent nanocomposites repelling Pseudomonas aeruginosa biofilms.

Preventing bacteria from adhering to material surfaces is an important technical problem and a major cause of infection. One of nature's defense strategies against bacterial colonization is based on the biohalogenation of signal substances that interfere with bacterial communication. Biohalogenation is catalyzed by haloperoxidases, a class of metal-dependent enzymes whose activity can be mimicked by ceria nanoparticles. Transparent CeO2/polycarbonate surfaces that prevent adhesion, proliferation, and spread of Pseudomonas aeruginosa PA14 were manufactured. Large amounts of monodisperse CeO2 nanoparticles were synthesized in segmented flow using a high-throughput microfluidic benchtop system using water/benzyl alcohol mixtures and oleylamine as capping agent. This reduced the reaction time for nanoceria by more than one order of magnitude compared to conventional batch methods. Ceria nanoparticles prepared by segmented flow showed high catalytic activity in halogenation reactions, which makes them highly efficient functional mimics of haloperoxidase enzymes. Haloperoxidases are used in nature by macroalgae to prevent formation of biofilms via halogenation of signaling compounds that interfere with bacterial cell-cell communication ("quorum sensing"). CeO2/polycarbonate nanocomposites were prepared by dip-coating plasma-treated polycarbonate panels in CeO2 dispersions. These showed a reduction in bacterial biofilm formation of up to 85% using P. aeruginosa PA14 as model organism. Besides biofilm formation, also the production of the virulence factor pyocyanin in is under control of the entire quorum sensing systems P. aeruginosa. CeO2/PC showed a decrease of up to 55% in pyocyanin production, whereas no effect on bacterial growth in liquid culture was observed. This indicates that CeO2 nanoparticles affect quorum sensing and inhibit biofilm formation in a non-biocidal manner.

Zinc Oxide Nanoparticles Can Intervene in Radiation-Induced Senescence and Eradicate Residual Tumor Cells.

Despite recent advancements in tumor therapy, metastasis and tumor relapse remain major complications hindering the complete recovery of many cancer patients. Dormant tumor cells, which reside in the body, possess the ability to re-enter the cell cycle after therapy. This phenomenon has been attributed to therapy-induced senescence. We show that these cells could be targeted by the use of zinc oxide nanoparticles (ZnO NPs). In the present study, the properties of tumor cells after survival of 16 Gy gamma-irradiation were investigated in detail. Analysis of morphological features, proliferation, cell cycle distribution, and protein expression revealed classical hallmarks of senescent cells among the remnant cell mass after irradiation. The observed radiation-induced senescence was associated with the increased ability to withstand further irradiation. Additionally, tumor cells were able to re-enter the cell cycle and proliferate again after weeks. Treatment with ZnO NPs was evaluated as a therapeutical approach to target senescent cells. ZnO NPs were suitable to induce cell death in senescent, irradiation-resistant tumor cells. Our findings underline the pathophysiological relevance of remnant tumor cells that survived first-line radiotherapy. Additionally, we highlight the therapeutic potential of ZnO NPs for targeting senescent tumor cells.

Nanozymes in Nanofibrous Mats with Haloperoxidase-like Activity To Combat Biofouling.

Electrospun polymer mats are widely used in tissue engineering, wearable electronics, and water purification. However, in many environments, the polymer nanofibers prepared by electrospinning suffer from biofouling during long-term usage, resulting in persistent infections and device damage. Herein, we describe the fabrication of polymer mats with CeO2- x nanorods that can prevent biofouling in an aqueous environment. The embedded CeO2- x nanorods are functional mimics of natural haloperoxidases that catalyze the oxidative bromination of Br- and H2O2 to HOBr. The generated HOBr, a natural signaling molecule, disrupted the bacterial quorum sensing, a critical step in biofilm formation. The polymer fibers provide porous structures with high water wettability, and the embedded cerium oxide nanozymes act as a catalyst that can efficiently trigger oxidative bromination, as shown by a haloperoxidase assay. Additionally, the embedded nanozymes enhance the mechanical property of polymer mats, as shown by a single-fiber bending test using atomic force microscopy. We envision that the fabricated polymer mats with CeO2- x nanorods may be used to provide mechanically robust coatings with antibiofouling properties.