EMX2 gene expression predicts liver metastasis and survival in colorectal cancer.

BACKGROUND: The Empty Spiracles Homeobox (EMX-) 2 gene has been associated with regulation of growth and differentiation in neuronal development. While recent studies provide evidence that EMX2 regulates tumorigenesis of various solid tumors, its role in colorectal cancer remains unknown. We aimed to assess the prognostic significance of EMX2 expression in stage III colorectal adenocarcinoma. METHODS: Expression levels of EMX2 in human colorectal cancer and adjacent mucosa were assessed by qRT-PCR technology, and results were correlated with clinical and survival data. siRNA-mediated knockdown and adenoviral delivery-mediated overexpression of EMX2 were performed in order to investigate its effects on the migration of colorectal cancer cells in vitro. RESULTS: Compared to corresponding healthy mucosa, colorectal tumor samples had decreased EMX2 expression levels. Furthermore, EMX2 down-regulation in colorectal cancer tissue was associated with distant metastasis (M1) and impaired overall patient survival. In vitro knockdown of EMX2 resulted in increased tumor cell migration. Conversely, overexpression of EMX2 led to an inhibition of tumor cell migration. CONCLUSIONS: EMX2 is frequently down-regulated in human colorectal cancer, and down-regulation of EMX2 is a prognostic marker for disease-free and overall survival. EMX2 might thus represent a promising therapeutic target in colorectal cancer.

Light-addressable capsules as caged compound matrix for controlled triggering of cytosolic reactions.

Release me: polyelectrolyte capsules with different cargo in their cavities and plasmonic and magnetic nanoparticles in their walls were synthesized. Enzymatic reactions were triggered inside cells by light-mediated opening of two individual capsules containing either an enzyme or its substrate, by using photothermal heating. Furthermore, this technique allows controlled release of mRNA from capsules, thereby resulting in synthesis of green fluorescent protein (GFP).

Multiplexed sensing and imaging with colloidal nano- and microparticles.

Sensing and imaging with fluorescent, plasmonic, and magnetic colloidal nano- and microparticles have improved during the past decade. In this review, we describe the concepts and applications of how these techniques can be used in the multiplexed mode, that is, sensing of several analytes in parallel or imaging of several labels in parallel.

NIR-light triggered delivery of macromolecules into the cytosol.

Light-responsive microcapsules constructed by layer-by-layer self-assembly are used as microcarriers to deliver different macromolecules inside cells. The microcapsules carry the macromolecules as cargo in their cavity, while their walls are modified with agglomerated gold nanoparticles. Microcapsules are incorporated by living cells and are then located in lysosomal compartments. Controlled release of the encapsulated material from the interior of the capsule to the cytosol is possible upon NIR-light irradiation. This is based on local heating of the gold nanoparticles upon NIR light and disruption of the capsule wall, what results on release of encapsulated materials. We illustrate several key advances in controlled release induced by light. First, we demonstrate that capsules can be opened individually, which allows for sequentially releasing cargo from different capsules within one single cell. Second, by using a pH-indicator as cargo the claim of release from the acidic lysosomal compartments to the neutral cytosol is experimentally evident which until now has been only speculated. Third, green fluorescent protein (GFP) is released to the cytosol while retaining its functionality. This demonstrates that proteins can be released without destruction by the local heating. Fourth, GFP is also administered in biodegradable capsules, which leads to a different release mechanism compared to externally triggering for light-responsive microcapsules.

Multiplexed sensing of ions with barcoded polyelectrolyte capsules.

Multiplexed detection of analytes is a challenge for numerous medical and biochemical applications. Many fluorescent particulate devices are being developed as ratiometric optical sensors to measure the concentration of intracellular analytes. The response of these sensors is based on changes of the emission intensity of analyte-sensitive probes, entrapped into the carrier system, which depends on the concentration of a specific analyte. However, there are a series of technical limits that prevent their use for quantitative detection of several analytes in parallel (e.g., emission crosstalk between different sensor molecules). Here we demonstrate that double-wall barcoded sensor capsules can be used for multiplexed analysis of proton, sodium, and potassium ions. The sensor detection methodology is based on porous microcapsules which carry ion-sensitive probes in their inner cavity for ion detection and a unique QD barcode in their outermost wall as tag for identification of individual sensors. The engineering of QD barcodes to capsules walls represents a promising strategy for optical multianalyte determination.

How colloidal nanoparticles could facilitate multiplexed measurements of different analytes with analyte-sensitive organic fluorophores.

Multiplexed measurements of several analytes in parallel using analyte-sensitive organic fluorophores can be hampered by spectral overlap of the different fluorophores. The authors discuss how nanoparticles can help to overcome this problem. First, different organic fluorophores can be separated spatially by confining them to separate containers, each bearing a nanoparticle-based barcode. Second, by coupling different fluorophores to nanoparticles with different fluorescence lifetimes that serve as donors for excitation transfer, the effective fluorescence lifetime of the organic fluorophores as acceptors can be tuned by fluorescence resonance energy transfer (FRET). Thus, the fluorophores can be distinguished by their effective lifetimes. This is an example of how the modification of classical functional materials has already yielded improved and even new functionalities by the integration of nanoparticles with hybrid materials. We outline future opportunities in this area.

LbL multilayer capsules: recent progress and future outlook for their use in life sciences.

In this review we provide an overview of the recent progress in designing composite polymer capsules based on the Layer-by-Layer (LbL) technology demonstrated so far in material science, focusing on their potential applications in medicine, drug delivery and catalysis. The benefits and limits of current systems are discussed and the perspectives on emerging strategies for designing novel classes of therapeutic vehicles are highlighted.