Inorganic enzyme? Ceria nanoparticles exhibit unique oxidase‐like activity at acidic pH values. These redox catalysts can be used in immunoassays (ELISA) when modified with targeting ligands (see picture; light blue and yellow structures are nanoparticles with attached ligands). This modification allows both for binding and for detection by the catalytic oxidation of sensitive colorimetric dyes (e.g. TMB).

Cerium oxide nanoparticles (nanoceria) have shown great potential as antioxidant and radioprotective agents for applications in cancer therapy. Recently, various polymer-coated nanoceria preparations have been developed to improve their aqueous solubility and allow for surface functionalization of these nanoparticles. However, the interaction of polymer-coated nanoceria with cells, their uptake mechanism and subcellular localization are poorly understood. Herein, we engineered polymer-coated cerium oxide nanoparticles with different surface charge (positive, negative and neutral) and studied their internalization and toxicity in normal and cancer cell lines. Results showed that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle's surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticles’ cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cells. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells. Taken together, these results indicate that the differential surface-charge-dependent localization of nanoceria in normal and cancer cells plays a critical role in the nanoparticles’ toxicity profile.

A biocompatible, multimodal and theranostic functional IONPs was synthesized using a novel waterbased method and exerted excellent properties for targeted cancer therapy, optical and magnetic resonance imaging (MRI). For the first time, a facile, modified solvent diffusion method is used for the co-encapsulation of both an anti-cancer drug and near infrared dyes. The resulting folate-derivatized theranostics nanoparticles could allow for targeted optical/MR-imaging and targeted killing of folate expressing cancer cells.

Anorganisches Enzym? Ceroxidnanopartikel zeigen einzigartige Oxidaseaktivität bei niedrigen pH‐Werten. Diese Redoxkatalysatoren können in Immunassays (ELISA) verwendet werden, wenn sie mit geeigneten Liganden modifiziert sind (siehe Bild; hellblau, gelb: Nanopartikel mit Liganden). Diese Modifizierung ermöglicht sowohl die Bindung als auch die Detektion durch katalytische Oxidation empfindlicher kolorimetrischer Farbstoffe (z. B. TMB).

4 7 F Fluorescence-based detection techniques have been widely used in modern biochemical research and disease diagnosis. For the detection of trace levels of analytes, organic fluorophores are commonly exploited as signal transduction tools. Although these fluorophores are versatile and easy to use, their molecular nature determines their limitations. In most cases, only one or a few fluorophores can signal one biomolecule recognition event, and typically, only a limited number of fluorophores can be attached to a biomolecule without interfering with its binding specificity or causing it to precipitate. As a consequence, sample analysis can be particularly difficult when trace amounts of biological analytes are present, and the additional steps required for signal amplification can be time-consuming and impede analyte quantitation.When exposed to a continuous light source, organic fluorophores are not very photostable. In addition, the complex environment inside living cells can increase the vulnerability of organic fluorophores to degradation and photobleaching. These two factors can result in false-positive and false-negative signals and can affect prolonged cell monitoring and 3-D optical sectioning imaging. Moreover, although most organic fluorophores can be conjugated with biomolecules, such as DNA and proteins, a different conjugation chemistry must be used to attach the organic dye to a given biomolecule of interest; this chemistry can be too difficult, time-consuming, and/or expensive for routine applications. All of these limitations have greatly hindered the use of fluorophores for in vitro assays and in vivo cellular imaging.The rapidly evolving field of nanoscience and nanotechnology has opened up a promising era in new biomarker development, in which nanoparticles of various shapes, sizes, and compositions have been successfully used in bioimaging, labeling, and sensing because of their unique optical properties, high surface-to-volume ratio, and other size-dependent qualities (1-8). With manipulated composition and surface modification, these nanoparticle probes have enhanced the fluorescence signal, increased sensitivity, prolonged detection time, and generated better reproducibility.Quantum dots (QDs) and dye-doped nanoparticles are representative fluorescent nanoparticle probes of increasing research interest. QDs are ultrasmall (usually 1-10 nm in diameter), bright (20ϫ brighter than most organic fluorophores), and highly photostable nanocrystalline semiconductors. Their broad excitation spectra, along with narrow, symmetric, size-tunable fluorescence emission spanning the UV to NIR, make them ideal for multiplex analysis (simultaneous detection of multiple an-

Herein we describe the design and synthesis of a folate-doxorubicin conjugate with activatable fluorescence and activatable cytotoxicity. In this study we discovered that the cytotoxicity and fluorescence of doxorubicin are quenched (OFF) when covalently linked with folic acid. Most importantly, when the conjugate is designed with a disulfide bond linking the targeting folate unit and the cytotoxic doxorubicin, a targeted activatable prodrug is obtained that becomes activated (ON) within the cell by glutathione-mediated dissociation and nuclear translocation, showing enhanced fluorescence and cellular toxicity. In our novel design folic acid acted as both a targeting ligand for the folate receptor as well as a quencher for doxorubicin fluorescence.

Infectious diseases are still a major healthcare problem. From food intoxication and contaminated water, to hospital-acquired diseases and pandemics, infectious agents cause disease throughout the world. Despite advancements in pathogens’ identification, some of the gold-standard diagnostic methods have limitations, including laborious sample preparation, bulky instrumentation and slow data readout. In addition, new field-deployable diagnostic modalities are urgently needed in first responder and point of care applications. Apart from compact, these sensors must be sensitive, specific, robust and fast, in order to facilitate detection of the pathogen even in remote rural areas. Considering these characteristics, researchers have utilized innovative approaches by employing the unique properties of nanomaterials in order to achieve detection of infectious agents, even in complex media like blood. From gold nanoparticles and their plasmonic shifts to iron oxide nanoparticles and changes in magnetic properties, detection of pathogens, toxins, antigens and nucleic acids has been achieved with impressive detection thresholds. Additionally, as bacteria become resistant to antibiotics, nanotechnology has achieved the rapid determination of bacterial drug susceptibility and resistance using novel methods, such as amperometry and magnetic relaxation. Overall, these promising results hint to the adoption of nanotechnology-based diagnostics for the diagnosis of infectious diseases in diverse settings throughout the globe, preventing epidemics and safeguarding human and economic wellness.

The reliable and sensitive detection of cancer-specific biomarkers is important for the diagnosis and treatment of cancer. Hence, detection of these biomarkers has to be reliably and rapidly performed in diverse settings. A limitation of the conventional biomarker-screening method of ELISA is the employment of labile components, such as hydrogen peroxide and horseradish peroxidase. Previously, we reported that nanoceria is able to oxidize various colorimertic dyes at acidic pH, such as TMB and AzBTS, and an assay was designed for screening the folate receptor. Herein, we show that the ability of nanoceria to oxidize a substrate can be tuned by modulating the pH. Results showed that nanoceria can oxidize the non-fluorescent substrate ampliflu, either to the very stable fluorescent product resorufin at pH 7.0 or to the non-fluorescent resazurin at pH 4.0. Based on these findings, we conjugated Protein G to immobilize antibodies on the surface of nanoceria, in order to detect the expression of prototypic cancer biomarkers at pH 7.0, such as the folate receptor and EpCAM. We found that within 3 h, nanoceria identified the expression of the folate receptor and EpCAM on lung carcinoma and breast adenocarcinoma cells respectively. Traditional ELISA had a readout time of 15 h and a higher detection threshold, while requiring multiple washing steps. Considering these results and nanoceria’s ability to oxidize ampliflu to its stable fluorescent product at neutral pH, the use of antibody-carrying nanoceria in the lab and point-of-care molecular diagnostics is anticipated.