Publications by authors named "James F Leary"

Recent breakthroughs in nanoparticle research have led to improved drug delivery and have overcome problems associated with normal drug delivery methods. Optimizing the design of nanoparticles in terms of controlled size, shape, and surface chemistry of nanoparticles can maximize the therapeutic efficacy. To maximize therapeutic effects, advanced formulation and fabrication methods have been developed.

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While current imaging modalities, such as magnetic resonance imaging (MRI), computed tomography, and positron emission tomography, play an important role in detecting tumors in the body, no single-modality imaging possesses all the functions needed for a complete diagnostic imaging, such as spatial resolution, signal sensitivity, and tissue penetration depth. For this reason, multimodal imaging strategies have become promising tools for advanced biomedical research and cancer diagnostics and therapeutics. In designing multimodal nanoparticles, the physicochemical properties of the nanoparticles should be engineered so that they successfully accumulate at the tumor site and minimize nonspecific uptake by other organs.

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Oligonucleotide-functionalized nanoparticles (NPs) are promising agents for nanomedicine, but the potential in vitro nanotoxicity that may arise from such conjugates has yet to be evaluated in a dose response manner. Since nanomedicine functions on the single-cell level, measurements of nanotoxicity should also be performed as such. In vitro single-cell nanotoxicity assays based on scanning image cytometry are used to study a specific type of oligo-functionalized NP, "nanobarcoded" superparamagnetic iron oxide NPs (NB-SPIONs).

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Neurological injury, such as spinal cord injury, has a secondary injury associated with it. The secondary injury results from the biological cascade after the primary injury and affects previous uninjured, healthy tissue. Therefore, the mitigation of such a cascade would benefit patients suffering a primary injury and allow the body to recover more quickly.

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Iron oxide nanoparticles (IOs) are intrinsically theranostic agents that could be used for magnetic resonance imaging (MRI) and local hyperthermia or tissue thermal ablation. Yet, effective hyperthermia and high MR contrast have not been demonstrated within the same nanoparticle configuration. Here, magnetic nanoconstructs are obtained by confining multiple, ∼ 20 nm nanocubes (NCs) within a deoxy-chitosan core.

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The concept of personalized medicine has recently emerged as a promising way to address unmet medical needs. Due to the limitations of standard diagnostic and therapeutic strategies, the disease treatment is moving towards tailored treatment for individual patients, considering the inter-individual variability in therapeutic response. Theranostics, which involves the combination of therapy and diagnostic imaging into a single system, may fulfill the promise of personalized medicine.

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While nanoparticles are usually designed for targeted drug delivery, they can also simultaneously provide diagnostic information by a variety of in vivo imaging methods. These diagnostic capabilities make use of specific properties of nanoparticle core materials. Near-infrared fluorescent probes provide optical detection of cells targeted by real-time nanoparticle-distribution studies within the organ compartments of live, anesthetized animals.

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Imaging techniques including computed tomography, magnetic resonance imaging, and positron emission tomography (PET) offer many potential benefits to diagnosis and treatment of cancers. Each method has its own strong and weak points. Therefore, multimodal imaging techniques have been highlighted as an alternative method for overcoming the limitations of each respective imaging method.

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We present a disease-on-a-chip model in which cancer grows within phenotypically normal breast luminal epithelium on semicircular acrylic support mimicking portions of mammary ducts. The cells from tumor nodules developing within these hemichannels are morphologically distinct from their counterparts cultured on flat surfaces. Moreover, tumor nodules cocultured with the luminal epithelium in hemichannels display a different anticancer drug sensitivity compared to nodules cocultured with the luminal epithelium on a flat surface and to monocultures of tumor nodules.

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Preventive actions for chronic diseases hold the promise of improving lives and reducing healthcare costs. For several diseases, including breast cancer, multiple risk and protective factors have been identified by epidemiologists. The impact of most of these factors has yet to be fully understood at the organism, tissue, cellular and molecular levels.

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Intestinal acyl-CoA:diacylglycerol acyltransferase 2 (DGAT2) is important in the cellular and physiological responses to dietary fat. To determine the effect of increased intestinal DGAT2 on cellular and physiological responses to acute and chronic dietary fat challenges, we generated mice with intestine-specific overexpression of DGAT2 and compared them with intestine-specific overexpression of DGAT1 and wild-type (WT) mice. We found that when intestinal DGAT2 is present in excess, triacylglycerol (TG) secretion from enterocytes is enhanced compared to WT mice; however, TG storage within enterocytes is similar compared to WT mice.

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Background: Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating an NP formulation for nanomedicine. Current methods to determine NP biodistribution are greatly inadequate, due to their limited detection thresholds. Herein, proof of concept of a novel method for improved NP detection based on in situ polymerase chain reaction (ISPCR), coined "nanobarcoding," is demonstrated.

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The earliest impact of nanomedicine in ophthalmology is likely to involve the areas of biopharmaceuticals, implantable materials (e.g. tissue regeneration scaffolds, bioresorbable materials), implantable devices (e.

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Properly evaluating the nanotoxicity of nanoparticles involves much more than bulk-cell assays of cell death by necrosis. Cells exposed to nanoparticles may undergo repairable oxidative stress and DNA damage or be induced into apoptosis. Exposure to nanoparticles may cause the cells to alter their proliferation or differentiation or their cell-cell signaling with neighboring cells in a tissue.

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One difficulty of diagnosing and treating cancer is that it is very challenging to detect cancers in the early stages before metastasis occurs. A variety of imaging modalities needs to be used from non-invasive, moderate resolution modalities, such as magnetic resonance imaging (MRI) to very high-resolution (e.g.

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ErbB4 is a member of the ErbB family of receptor tyrosine kinases. This family includes ErbB2 (HER2/Neu), a validated therapeutic target in breast cancer. Several studies indicate that ErbB4 functions as a tumor suppressor in breast cancer, whereas others indicate that ErbB4 functions as an oncogene.

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Obesity results in abnormally high levels of triglyceride (TG) storage in tissues such as liver, heart, and muscle, which disrupts their normal functions. Recently, we found that lean mice challenged with high levels of dietary fat store TGs in cytoplasmic lipid droplets in the absorptive cells of the intestine, enterocytes, and that this storage increases and then decreases over time after an acute dietary fat challenge. The goal of this study was to investigate the effects of obesity on intestinal TG metabolism.

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Tumor-targeted imaging and therapy have been the challenging issue in the clinical field. Herein, we report tumor-targeting hyaluronic acid nanoparticles (HANPs) as the carrier of the hydrophobic photosensitizer, chlorin e6 (Ce6) for simultaneous photodynamic imaging and therapy. First, self-assembled HANPs were synthesized by chemical conjugation of aminated 5β-cholanic acid, polyethylene glycol (PEG), and black hole quencher3 (BHQ3) to the HA polymers.

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Regenerative medicine deals with the repair or the replacement of tissues and organs using advanced materials and methodologies. Regenerative nanomedicine uses nanoparticles containing gene transcription factors and other modulating molecules that allow reprogramming of cells in vivo as well as nanomaterials to induce selective differentiation of neural progenitor cells and to create neural-mechanical interfaces. In this article, we consider some applications of nanotechnology that may be useful for the treatment of degenerative retinal diseases, for example, use of nanoparticles for drug and gene therapy, use of nanomaterials for neural interfaces and extracellular matrix construction for cell-based therapy and neural prosthetics, and the use of bionanotechnology to re-engineer proteins and cell behavior for regenerative medicine.

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The wound healing assay is a commonly used technique to measure cell motility and migration. Traditional methods of performing the wound healing assay suffer from low throughput and a lack of quantitative data analysis. We have developed a new method to perform a high-throughput wound healing assay that produces quantitative data using the LEAP™ instrument.

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Herein, we developed the photosensitizer, protoporphyrin IX (PpIX), conjugated glycol chitosan (GC) nanoparticles (PpIX-GC-NPs) as tumor-homing drug carriers with cellular on/off system for photodynamic imaging and therapy, simultaneously. In order to prepare PpIX-GC-NPs, hydrophobic PpIXs were chemically conjugated to GC polymer and the amphiphilic PpIX-GC conjugates formed a stable nanoparticle structure in aqueous condition, wherein conjugated PpIX molecules formed hydrophobic inner-cores and they were covered by the hydrophilic GC polymer shell. Based on the nanoparticle structure, PpIX-GC-NPs showed the self-quenching effect that is 'off' state with no fluorescence signal and phototoxicity with light exposure.

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Nanotechnology involves the creation and use of materials and devices at the size scale of intracellular structures and molecules, and involves systems and constructs in the order of <100 nm. The aim of nanomedicine is the comprehensive monitoring, control, construction, repair, defence, and improvement of human biological systems at the molecular level, using engineered nanodevices and nanostructures that operate massively in parallel at the single-cell level, ultimately to achieve medical benefit. In this review we consider general principles of nanotechnology as applied to nanomedicine (e.

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SIZE matters… the size of the scalpel determines the precision of the surgery. Nanotechnology affords us the chance to construct nanotools that are on the size scale of molecules, allowing us to treat each cell of the human body as a patient. Nanomedicine will allow for eradication of disease at the single-cell level.

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Purpose: To review the fields of nanotechnology and nanomedicine as they relate to the development of treatments for vision-threatening disorders.

Design: Perspective following literature review.

Methods: Analysis of relevant publications in the peer-reviewed scientific literature.

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