Strategies for enhanced gene delivery to the central nervous system.

The delivery of genes to the central nervous system (CNS) has been a persistent challenge due to various biological barriers. The blood-brain barrier (BBB), in particular, hampers the access of systemically injected drugs to parenchymal cells, allowing only a minimal percentage (<1%) to pass through. Recent scientific insights highlight the crucial role of the extracellular space (ECS) in governing drug diffusion.

Tarlov Cysts and Premature Ejaculation.

Tarlov cysts adjacent to the spinal cord are usually asymptomatic and found incidentally via magnetic resonance imaging. On rare occasions, they increase in size to produce symptoms resembling disk herniation. We report a rare case of a sacral cyst resulting in premature ejaculation in a 32-year-old man who presented with pelvic pain and acquired premature ejaculation.

Clinical gene therapy development for the central nervous system: Candidates and challenges for AAVs.

Many diseases affecting the central nervous system (CNS) are deadly but less understood, leading to impaired mental and motor capabilities and poor patient prospects. Gene therapy is a promising therapeutic modality for correcting many genetic disorders, expanding in breadth and scope with further advances. This review summarizes the candidate CNS disorders for gene therapy, mechanisms of gene therapy, and recent clinical advances and limitations of gene therapy in CNS disorders.

Integrated Imaging Methodology Detects Claudin-1 Expression in Premalignant Nonpolypoid and Polypoid Colonic Epithelium in Mice.

Objectives: Conventional colonoscopy with white light illumination detects colonic adenomas based on structural changes alone and is limited by a high miss rate. We aim to demonstrate an integrated imaging strategy that combines wide-field endoscopy and confocal endomicroscopy in real time to visualize molecular expression patterns in vivo to detect premalignant colonic mucosa.

Methods: A peptide specific for claudin-1 is labeled with Cy5.

Dual-modal in vivo fluorescence and photoacoustic imaging using a heterodimeric peptide.

A heterodimeric peptide labeled with IRDye800 is used to perform dual-modal imaging of human esophageal xenograft tumors in vivo. Fluorescence and photoacoustic images provide complementary visualization of tumor dimensions in planar and sagittal views, respectively, demonstrating promise for targeted cancer diagnosis and staging.

Ultrashort Carbon Nanotubes That Fluoresce Brightly in the Near-Infrared.

The intrinsic near-infrared photoluminescence observed in long single-walled carbon nanotubes is known to be quenched in ultrashort nanotubes due to their tiny size as compared to the exciton diffusion length in these materials (>100 nm). Here, we show that intense photoluminescence can be created in ultrashort nanotubes (∼40 nm length) upon incorporation of exciton-trapping sp defect sites. Using super-resolution photoluminescence imaging at <25 nm resolution, we directly show the preferential localization of excitons at the nanotube ends, which separate by less than 40 nm and behave as independent emitters.

Multiplexed Targeting of Barrett's Neoplasia with a Heterobivalent Ligand: Imaging Study on Mouse Xenograft in Vivo and Human Specimens ex Vivo.

Esophageal adenocarcinoma (EAC) is a molecularly heterogeneous disease that is rising rapidly in incidence and has poor prognosis. We developed a heterobivalent peptide to target detection of early Barrett's neoplasia by combining monomer heptapeptides specific for either EGFR or ErbB2 in a heterodimer configuration. The structure of a triethylene glycol linker was optimized to maximize binding interactions to the surface receptors on cells.

Evaluation of Different Single-Walled Carbon Nanotube Surface Coatings for Single-Particle Tracking Applications in Biological Environments.

Fluorescence imaging of biological systems down to the single-molecule level has generated many advances in cellular biology. For applications within intact tissue, single-walled carbon nanotubes (SWCNTs) are emerging as distinctive single-molecule nanoprobes, due to their near-infrared photoluminescence properties. For this, SWCNT surfaces must be coated using adequate molecular moieties.

In vivo near-infrared imaging of ErbB2 expressing breast tumors with dual-axes confocal endomicroscopy using a targeted peptide.

ErbB2 expression in early breast cancer can predict tumor aggressiveness and clinical outcomes in large patient populations. Accurate assessment with physical biopsy and conventional pathology can be limited by tumor heterogeneity. We aim to demonstrate real-time optical sectioning using a near-infrared labeled ErbB2 peptide that generates tumor-specific contrast in human xenograft breast tumors in vivo.

Detection of Sessile Serrated Adenomas in the Proximal Colon Using Wide-Field Fluorescence Endoscopy.

Background & Aims: Many cancers in the proximal colon develop via from sessile serrated adenomas (SSAs), which have flat, subtle features that are difficult to detect with conventional white-light colonoscopy. Many SSA cells have the V600E mutation in BRAF. We investigated whether this feature could be used with imaging methods to detect SSAs in patients.

Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain.

The brain is a dynamic structure with the extracellular space (ECS) taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the ECS, which constitutes a key microenvironment for cellular communication and the clearance of toxic metabolites. The spatial organization of the ECS varies during sleep, development and aging and is probably altered in neuropsychiatric and degenerative diseases, as inferred from electron microscopy and macroscopic biophysical investigations.

Toward the suppression of cellular toxicity from single-walled carbon nanotubes.

In the multidisciplinary fields of nanobiology and nanomedicine, single-walled carbon nanotubes (SWCNTs) have shown great promise due to their unique morphological, physical and chemical properties. However, understanding and suppressing their cellular toxicity is a mandatory step before promoting their biomedical applications. In light of the flourishing recent literature, we provide here an extensive review on SWCNT cellular toxicity and an attempt to identify the key parameters to be considered in order to obtain SWCNT samples with minimal or no cellular toxicity.

Optical detection of individual ultra-short carbon nanotubes enables their length characterization down to 10 nm.

Ultrashort single-walled carbon nanotubes, i.e. with length below ~30 nm, display length-dependent physical, chemical and biological properties that are attractive for the development of novel nanodevices and nanomaterials.

Single-molecule imaging in live cell using gold nanoparticles.

Optimal single particle tracking experiments in live cells requires small and photostable probes, which do not modify the behavior of the molecule of interest. Current fluorescence-based microscopy of single molecules and nanoparticles is often limited by bleaching and blinking or by the probe size. As an alternative, we present in this chapter the synthesis of a small and highly specific gold nanoprobe whose detection is based on its absorption properties.

Nonlinear photoluminescence spectroscopy of carbon nanotubes with localized exciton states.

We report distinctive nonlinear behavior of photoluminescence (PL) intensities from localized exciton states embedded in single-walled carbon nanotubes (SWNTs) at room temperature. We found that PL from the local states exhibits strong nonlinear behavior with increasing continuous-wave excitation power density, whereas free exciton PL shows only weak sublinear behavior. The strong nonlinear behavior was observed regardless of the origin of the local states and found to be nearly independent of the local state density.

Noncovalent Functionalization of Boron Nitride Nanotubes in Aqueous Media Opens Application Roads in Nanobiomedicine.

Boron nitride nanotubes (BNNTs) are of intense scientific interest due to their unique physiochemical properties and prospective applications in various nanotechnologies, particularly nanobiomedicine. A critical problem hampering the application processing of BNNTs is the outer sidewall functionalization, which is primarily acquired to lead BNNTs dispersible in various solvents. Furthermore, the surface of BNNTs should be intelligently designed and precisely controlled to satisfy the specific demands of different applications.

Noncovalent functionalization of disentangled boron nitride nanotubes with flavin mononucleotides for strong and stable visible-light emission in aqueous solution.

Strong and stable visible-light-emitting boron nitride nanotube (BNNT)/biomolecule nanohybrids were successfully fabricated via noncovalent functionalization of BNNTs with flavin mononucleotides (FMN). Atomic force microscopy showed excellent dispersion of the nanohybrids in aqueous solution. Infrared absorption spectroscopy revealed strong π-π stacking interactions between FMN and BNNT sidewalls.

Isolation of individual boron nitride nanotubes via peptide wrapping.

The isolation of individual boron nitride nanotubes (BNNTs) in aqueous phases has been achieved for the first time from raw materials based on the combination of peptide wrapping with a sonication procedure. Atomic force microscopic observations revealed the representative height and length of individual BNNTs. Fluorescence and infrared absorption spectra suggested the strong pi-pi interactions between BNNTs and the peptide.