University of Cincinnati

Cincinnati Children's Hospital Medical Center

The Ohio State University

Other

Children's Hospital Research Foundation

Molecular Targeting Technologies. Inc.

Xiaoyang Qi

Brian D Gray

Koon Y Pak

Harold W Davis

Balveen Kaur

Jeffrey Wojton

Andrei Kogan

Daria Narmoneva

Matthew J Flick

Ahmet Kaynak

Nikhil Shukla

Sherry L Thornton

Koon Yan Pak

Compositions that include a phenol group conjugated to a lipid group to form a phenolic lipid. The lipid group may include a fluorophore and at least one lipid anchor. The lipid anchor may have a carbon number that ranges between 7 carbon atoms and 22 carbon atoms. Also, included are methods of making and using such phenolic lipids. Further included are methods of iodinating hydrophobic compounds such as phenolic lipids in aqueous based iodination protocols. Cosolvent formulations for use in such methods are also described.

Iodinated phenolic lipids and methods and cosolvent systems for iodination of phenolic lipids

A method of treating cancer is disclosed. The method involves applying one or more direct current electric fields (DC-EFs) to a subject and administering to the subject an additional treatment selected from the group consisting of radiation, an effective amount of one or more chemotherapy agents, SapC-DOPS, anti-phosphatidylserine targeted drugs, and combinations thereof.

Combination therapy of electric fields and an additional treatment for cancer and imaging

A method of inducing cell death in a glioblastoma multiforme cancer cell is provided, the method comprising administering to the cell a combination of therapeutic agents comprising: saposin C and dioleoylphosphatidylserine (SapC-DOPS), and nucleolin aptamer AS1411, wherein cell death of the cancer cell is induced. Also provided are methods of treating glioblastoma multiforme, methods of inhibiting growth of a glioblastoma multiforme tumor, kits, and pharmaceutical compositions comprising SapC-DOPS and AS1411.

Combination of AS1411 and SAPC-DOPS for the treatment of glioblastoma multiforme

The present invention provides compositions and methods useful for treating cancers such as glioblastoma. SapC-DOPS was found to be synergistically effective at inducing cell death when administered in conjunction with rampamycin. SapC-DOPS/rapamycin combination therapy allows physicians to give lower doses of each drug and achieve better therapeutic efficacy. The compositions also allow for less toxicity and fewer off-target effects. Related methods and materials are also provided herein.

Materials and methods useful for treating glioblastoma

Compositions and methods for treating subjects with disorders characterized by hyper-proliferating cells such as tumors and cancers are provided. The compositions comprise agents that are combinations of saposin C (or prosaposin-related polypeptides) and phospholips (or inner leaflet components). This anti-tumor agent is administered in the methods of the invention according to a dosing regimen. Administering an agent of the invention results in a positive therapeutic response in a subject with a tumor.

Saposin C-DOPS: a novel anti-tumor agent

The present invention provides compositions and methods useful for treating cancers such as glioblastoma. SapC-DOPS was found to be synergistically effective at inducing cell death when administered in conjunction with rapamycin. SapC-DOPS/rapamycin combination therapy allows physicians to give lower doses of each drug and achieve better therapeutic efficacy. The compositions also allow for less toxicity and fewer off-target effects. Related methods and materials are also provided herein.

Materials and methods useful for treating glioblastorna

The present disclosure demonstrates that a nanovesicle comprising a membrane-associated lysosomal protein (saposin C; 'SapC') incorporated into a phospholipid has a high fusogenic affinity for phosphatidylserine-rich domains on the surfaces of target cell membranes. It is believed that the nanovesicles target surface exposed phosphatidylserine on the membranes of cells associated with arthritis, allowing for detection of local tissue damage associated with arthritis. In plasma membranes, phosphatidylserine is normally present only on the inner leaflet but is 'flipped' to the outer leaflet upon the presence of cell damage. Incorporation of the fluorophore in the nanovesicles allows for the in vivo visualization of the fluorophore in targeted tissue and provides a technique to detect and evaluate the onset and progression of arthritic disease in an animal. Furthermore, the use of the nanovesicle in optical imaging methods provides great promise for analyzing events occurring early in the pathogenesis of arthritis and arthritic disease.

Method for imaging a site of arthritis in an animal

The present invention comprises a method for delivering pharmaceutical and/or imaging agents within and/or through the dermal, mucosal and other cellular membranes, and across the blood-brain barrier, utilizing a fusogenic protein. The fusogenic protein is associated with a phospholipid membrane, such as a liposome. The liposome may include dioleoylphosphatidylserine, a negatively charged long-chain lipid. Alternatively, the liposome is comprised of a mixture of negatively charged long-chain lipids, neutral long-chain lipids, and neutral short-chain lipids. Preferred fusogenic proteins include saposin C and other proteins, polypeptides and peptide analogs derived from saposin C. The active agent contained within the liposome may comprise biomolecules and/or organic molecules. This technology can be used for both cosmetic and medicinal applications in which the objective is delivery of the active agent within and/or beneath biological membranes or across the blood-brain barrier and neuronal membranes.

Fusogenic properties of saposin C and related proteins and peptides for application to transmembrane drug delivery systems

Compositions and methods for treating subjects with disorders characterized by hyper-proliferating cells such as tumors and cancers are provided. The compositions comprise agents that are combinations of saposin C (or prosaposin-related polypeptides) and dioleoylphosphatidylserine (or inner leaflet components). This anti-tumor agent is administered in the methods of the invention according to a dosing regimen. Administering an agent of the invention results in a positive therapeutic response in a subject with a tumor.

The present invention comprises a method for delivering pharmaceutical agents within and/or through the dermal and mucosal membranes, utilizing a fusogenic protein. The fusogenic protein is associated with a phospholipid membrane, such as a liposome. The liposome contains the pharmaceutical agent. Preferred fusogenic proteins include saposin C and other proteins, polypeptides and peptide analogs derived from saposin C. The active agent contained within the liposome may comprise large biomolecules and/or small organic molecules. This technology can be used for both cosmetic and medicinal applications in which the objective is delivery of the active agent within and/or beneath the biological membrane.

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Cincinnati, OH, United States of America

Xiaoyang Qi