118 research outputs found
IDENTIFYING PATIENTS BY CT ANGIOGRAPHY WHO WOULD OR WOULD NOT BENEFIT FROM CORONARY ARTERIAL REVASCULARIZATION – INSIGHTS FROM THE CORE-64 INTERNATIONAL, MULTICENTER STUDY
Tuning a Polar Molecule for Selective Cytoplasmic Delivery by a pH (Low) Insertion Peptide
Drug molecules are typically hydrophobic and small in order to traverse membranes to reach cytoplasmic targets, but we have discovered that more polar molecules can be delivered across membranes using water-soluble, moderately hydrophobic membrane peptides of the pHLIP (pH low insertion peptide) family. Delivery of polar cargo molecules could expand the chemical landscape for pharmacological agents that have useful activity but are too polar by normal drug criteria. The spontaneous insertion and folding of the pHLIP peptide across a lipid bilayer seeks a free energy minimum, and insertion is accompanied by a release of energy that can be used to translocate cell-impermeable cargo molecules. In this study, we report our first attempt to tune the hydrophobicity of a polar cargo, phallacidin, in a systematic manner. We present the design, synthesis, and characterization of three phallacidin cargoes, where the hydrophobicity of the cargo was tuned by the attachment of diamines of various lengths of hydrophobic chains. The phallacidin cargoes were conjugated to pHLIP and shown to selectively inhibit the proliferation of cancer cells in a concentration-dependent manner at low pH
Comparative Study of Tumor Targeting and Biodistribution of pH (Low) Insertion Peptides (pHLIP® Peptides) Conjugated with Different Fluorescent Dyes
Purpose
Acidification of extracellular space promotes tumor development, progression, and invasiveness. pH (low) insertion peptides (pHLIP® peptides) belong to the class of pH-sensitive membrane peptides, which target acidic tumors and deliver imaging and/or therapeutic agents to cancer cells within tumors. Procedures
Ex vivo fluorescent imaging of tissue and organs collected at various time points after administration of different pHLIP® variants conjugated with fluorescent dyes of various polarity was performed. Methods of multivariate statistical analyses were employed to establish classification between fluorescently labeled pHLIP® variants in multidimensional space of spectral parameters.
Results
The fluorescently labeled pHLIP® variants were classified based on their biodistribution profile and ability of targeting of primary tumors. Also, submillimeter-sized metastatic lesions in lungs were identified by ex vivo imaging after intravenous administration of fluorescent pHLIP® peptide.
Conclusions
Different cargo molecules conjugated with pHLIP® peptides can alter biodistribution and tumor targeting. The obtained knowledge is essential for the design of novel pHLIP®-based diagnostic and therapeutic agents targeting primary tumors and metastatic lesions
64Cu-ATSM and 18FDG PET uptake and 64Cu-ATSM autoradiography in spontaneous canine tumors: comparison with pimonidazole hypoxia immunohistochemistry
Leading Neuroblastoma Cells To Die by Multiple Premeditated Attacks from a Multifunctionalized Nanoconstruct
Metabolic Shifts Induced by Fatty Acid Synthase Inhibitor Orlistat in Non-small Cell Lung Carcinoma Cells Provide Novel Pharmacodynamic Biomarkers for Positron Emission Tomography and Magnetic Resonance Spectroscopy
Simulated 50 % radiation dose reduction in coronary CT angiography using adaptive iterative dose reduction in three-dimensions (AIDR3D)
Quantification of three-dimensional computed tomography angiography for evaluating coronary luminal stenosis using digital subtraction angiography as the standard of reference
Coronary CT angiographic predictors of vasodilator induced myocardial ischemia: a comprehensive analysis
Cardiovascular Aspects of Radiolog
Coronary Arterial Stenosis Assessment versus Different Coronary Atherosclerotic Plaque Burden Indices by Computed Tomography Angiography for Detecting Hemodynamically Significant Coronary Artery Disease - Insights From the CORE320 International Study
Cardiovascular Aspects of Radiolog
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