Supramolecular Nucleic Acid-Based Organosilica Nanoparticles Responsive to Physical and Biological Inputs.

Organosilica nanoparticles that contain responsive organic building blocks as constitutive components of the silica network offer promising opportunities for the development of innovative drug formulations, biomolecule delivery, and diagnostic tools. However, the synthetic challenges required to introduce dynamic and multifunctional building blocks have hindered the realization of biomimicking nanoparticles. In this study, capitalizing on our previous research on responsive nucleic acid-based organosilica nanoparticles, we combine the supramolecular programmability of nucleic acid (NA) interactions with sol-gel chemistry. This approach allows us to create dynamic supramolecular bridging units of nucleic acids in a silica-based scaffold. Two peptide nucleic acid-based monoalkoxysilane derivatives, which self-assemble into a supramolecular bis-alkoxysilane through direct base pairing, were chosen as the noncovalent units inserted into the silica network. In addition, a bridging functional NA aptamer leads to the specific recognition of ATP molecules. In a one-step bottom-up approach, the resulting supramolecular building blocks can be used to prepare responsive organosilica nanoparticles. The supramolecular Watson-Crick-Franklin interactions of the organosilica nanoparticles result in a programmable response to external physical (i.e., temperature) and biological (i.e., DNA and ATP) inputs and thus pave the way for the rational design of multifunctional silica materials with application from drug delivery to theranostics.

Rapid, Cost-Effective Peptide/Nucleic Acid-Based Platform for Therapeutic Antibody Monitoring in Clinical Samples.

We demonstrate here a homogeneous assay, named NanoHybrid, for monoclonal antibody quantification directly in serum samples in a single-step format. NanoHybrid is composed of both synthetic peptide nucleic acids (PNAs) and nucleic acid strands conjugated to recognition elements and optical labels and is designed to allow fast fluorescence quantification of a therapeutic antibody. More specifically, we have characterized our analytical assay for the detection of trastuzumab (Herceptin), a monoclonal antibody (mAb) drug used for breast cancer treatment and for tumors overexpressing the HER2/neu protein. We show here that NanoHybrid is capable of performing fast drug quantification directly in blood serum. The results obtained with a pool of samples from breast cancer patients under trastuzumab treatment are compared with CE-IVD ELISA (enzyme-linked immunosorbent assay) showing a good agreement (Cohen's K = 0.729). Due to the modular nature of the NanoHybrid platform, this technology can be programmed to potentially detect and quantify any antibody for which a high-affinity recognition element has been characterized. We envision the application of NanoHybrid in a point-of-care (POC) drug monitoring system based on disposable kits for therapeutic drug management.

A Modular, DNA-Based Beacon for Single-Step Fluorescence Detection of Antibodies and Other Proteins.

A versatile platform for the one-step fluorescence detection of both monovalent and multivalent proteins has been developed. This system is based on a conformation-switching stem-loop DNA scaffold that presents a small-molecule, polypeptide, or nucleic-acid recognition element on each of its two stem strands. The steric strain associated with the binding of one (multivalent) or two (monovalent) target molecules to these elements opens the stem, enhancing the emission of an attached fluorophore/quencher pair. The sensors respond rapidly (<10 min) and selectively, enabling the facile detection of specific proteins even in complex samples, such as blood serum. The versatility of the platform was demonstrated by detecting five bivalent proteins (four antibodies and the chemokine platelet-derived growth factor) and two monovalent proteins (a Fab fragment and the transcription factor TBP) with low nanomolar detection limits and no detectable cross-reactivity.

Intrapetrous internal carotid artery dissection and essential thrombocythemia: what relationship? A case report.

Internal carotid artery (ICA) dissection is responsible for 10-20% of strokes in young and middle-aged patients. Isolated ICA dissection involving the intrapetrous carotid canal is particularly rare, and no case has been reported to describe an association between intrapetrous ICA dissection and essential thrombocythemia. We report a case of ischemic stroke in the presence of intrapetrous right ICA dissection and essential thrombocythemia. The diagnosis of essential thrombocythemia was performed by bone marrow biopsy. The essential thrombocythemia may cause endothelial dysfunction and predispose to vascular damage such as carotid artery dissection.