Leland Stanford Junior University

Other

Zhen Cheng

Sanjiv Sam Gambhir

Hongjie Dai

Richard H Kimura

Hao Chen

Xuechuan Hong

Alexander Antaris

Kai Cheng

Hongguang Liu

Kai Chen

Jennifer R Cochran

Matthew S Bogyo

Xiaoyuan Chen

Benjamin Joseph Hackel

Frederick T Chin

Bin Shen

Galia Blum

Zheng Miao

Gang Ren

Sri-rajasekhar Kothapalli

Alicia Berger

Robert Teed

Provided are delocalized lipophilic cation (DLC) compounds and methods of using such compounds. Also provided are pharmaceutical compositions that include a DLC compound. Provided methods include methods of killing cells and methods of fluorescently labeling mitochondria by contacting the cells with a DLC compound of the present disclosure. Also provided are methods of imaging cell mitochondria, methods of determining whether a patient has a mitochondria related disease, and methods of treating a patient for a mitochondria related disease. Kits that include compounds of the present disclosure are also provided.

Delocalized lipophilic cation compounds and methods of use thereof

The disclosure provides NIR-II imaging probes and methods of using the NIR-II imaging probes for dynamic in vivo tracking of cells, such as stem cells, or other substances. NIR-II imaging probes can include a biocompatible NIR-II dye molecule coupled to an organic, biocompatible protein carrier complex, including a carrier protein coupled to a cell-penetrating peptide.

NIR-II imaging probe and methods of using the NIR-II imaging probe for dynamic in vivo tracking

Disclosed is a small molecule dye for use in imaging in the near-infrared window, namely between 1000 nm-1700 nm wavelength. The present dyes are also useful for photoacoustic imaging and photothermal therapy. The dyes have a structure of a D-A-D (donor-acceptor-donor) fluorescent compound core and side chains rendering the compounds water soluble and easily conjugated to hydrophilic polymers and/or targeting ligands. Further disclosed is compound, CH1055 that can be PEGylated, conjugated to a targeting ligand, or conjugated to taurine. Key steps utilized to assemble the core structure of the target included a cross-Suzuki coupling reaction, iron reduction and N-thionylaniline induced ring closure. Four carboxylic acid groups were introduced into the donor-acceptor-donor (D-A-D) type fluorescent compound to impart a certain aqueous solubility and to allow facile conjugation to targeting ligands.

Small molecule dye for molecular imaging and photothermal therapy

Embodiments of the present disclosure provide for radionuclide probes, methods of using the radionuclide probes, methods of detecting an optical signal from radionuclides, methods of detecting an optical signal from a quantum dot(s) that receives optical energy from a radionuclide(s), system for analyzing optical energy emitted by a radionuclide(s), system for imaging a target within a living subject or a sample, methods of imaging a disease or condition, and the like.

Optical imaging probes, optical imaging systems, methods of optical imaging, and methods of using optical imaging probes

Compositions and methods of use thereof encompass engineered mesenchymal stem cells as a vehicle to deliver secreted tissue necrosis factor-RGD4C fusion polypeptides for tumor treatment, thereby reducing side effects of TNF. A reporter gene can be included in vector constructs to monitor the localization and viability of engineered MSCs after administration into a recipient animal. The genetically modified mesenchymal stem cell can comprise an expression cassette comprising a nucleic acid sequence operably linked to a gene expression promoter and encoding the heterologous fusion polypeptide comprising a tissue necrotic factor region and an integrin-binding region. Another aspect of the disclosure encompasses embodiments of a method of modulating the proliferation of a targeted population of tumor cells by delivering a population of the genetically modified mesenchymal stem cells to tumor cells, allowing the mesenchymal stem cells to express the heterologous polypeptide, thereby reducing the proliferative capacity of the tumor cells.

Imaging-aided gene therapy using mesenchymal stem cells as target-delivery vehicle

Engineered peptides that bind with high affinity (low equilibrium dissociation constant (Kd)) to the cell surface receptors of fibronectin (&#x3b1;&#x3b2;) or vitronectin (&#x3b1;&#x3b2;and &#x3b1;&#x3b2;integrins) are disclosed as useful as imaging tissue. These peptides are based on a molecular scaffold into which a subsequence containing the RGD integrin-binding motif has been inserted. The subsequence (RGD mimic) comprises about 9-13 amino acids, and the RGD contained within the subsequence can be flanked by a variety of amino acids, the sequence of which was determined by sequential rounds of selection (in vitro evolution). The molecular scaffold is preferably based on a knottin, e.g., EETI (Trypsin inhibitor 2 (Trypsin inhibitor II) (EETI-II) [Ecballium elaterium (Jumping cucumber)], AgRP (Agouti-related protein), and Agatoxin IVB, which peptides have a rigidly defined three-dimensional conformation. It is demonstrated that EETI tolerates mutations in other loops and that the present peptides may be used as imaging agents.

Imaging methods using engineered integrin binding peptides

Disclosed are peptides comprising a molecular scaffold portion and a loop portion that binds to integrin &#x3b1;&#x3b2;. This integrin is expressed on pancreatic tumors, making the peptides useful as imaging agents, among other uses. The peptides showed single-digit nanomolar dissociation constants similar to antibodies used clinically for imaging and therapy. The peptides rapidly accumulated in &#x3b1;&#x3b2;-positive tumors, which led to excellent tumor-to-normal contrast. The peptides are specific for the targeted integrin &#x3b1;&#x3b2;receptors expressed on orthotopic pancreatic tumors and various xenografts used. Additionally, pharmacokinetic-stabilization strategies endowed knots with rapid renal clearance, which significantly reduced off-target dosing.

Cystine knot peptides that bind alpha-V-beta-6 integrin

In accordance with the purpose(s) of the present disclosure, as embodied and broadly described herein, embodiments of the present disclosure, in one aspect, relate to methods of detecting the over-expression of epidermal growth factor receptor (EGFR) in a subject or sample, methods of diagnosing the presence of one or more angiogenesis related diseases or related biological events in a subject or sample, method of monitoring the progress of one or more angiogenesis related diseases or related biological events in a subject or sample, aF-FBEM-CYS-Zprobe, compositions including aF-FBEM-CYS-Zprobe, and pharmaceutical compositions including aF-FBEM-CYS-Zprobe and the like.

Imaging probes, methods of making imaging probes, and methods of imaging

Activity-based probes, which are specific for certain active cysteine proteases (caspase, cathepsin and legumain) and carry radioactive labels, are disclosed. The present probes comprise an acyloxymethyketone (AOMK) 'warhead' that binds only to active enzyme. The probes further comprise peptide-like structure that targets the probe to a specific cysteine protease or protease family, and a radiolabel on the probe, which is bound to the targeted enzyme. It has been found that the present probes are stable in vivo and give specific target images distinguishable over background. The preferred probes are labeled with a positron-emitting agent such asCu,I (SPECT) andTc (PET). The probes show in vivo half-life and stability well suited for imaging.

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Mountain View, CA, United States of America

Zhen Cheng