Image-Guided Therapy for Cancer
Patent Number: Pending
Executive Summary:
General Description:
Prof. Schultz’s lab at the University of Iowa has developed a novel image guided therapy for cancer. This invention relates to a class of molecules, tetra-arylethylene derivatives, that can specifically deliver drugs to mitochondria in tumor cells. Data demonstrates that this platform can be designed to accumulate in the melanoma mitochondrial membranes, disrupt tumor cell metabolism, and induce cell death. In addition, this invention allows for imaging the accumulation of the delivery vehicle molecule in cells, a novel property of lipophilic cations.
Scientific Progress:
The data suggest that lipophilic−cationic and polycationic−heteroaromatic tetra-arylethylenes pass through the hydrophobic mitochondrial membrane lipid bilayer, move down the negative mitochondrial membrane voltage potential, and preferentially imbed in the hyperpolarized mitochondria membranes of melanoma cells. Imaging of the accumulation of the tetra-arylethylene-based compounds demonstrated melanoma-cell specific accumulation with little accumulation in normal human fibroblasts as controls. It was further found that vinylpyridine derivative accumulation in melanoma cells disrupts the cellular oxidation state and induces increased toxicity in melanoma cells relative to nonmalignant cells.
Future Directions:
Strengths:
Patent Status:
Legal Status: Application pending
Publication PMID: 27902770, 27643916
Publications:
Schibler J, Tomanek-Chalkley AM, Reedy JL, Zhan F, Spitz DR, Schultz MK, Goel A. Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells. PLoS One. 2016 Nov 30;11(11):e0167323. doi: 10.1371/journal.pone.0167323. eCollection 2016.
Reedy JL, Hedlund DK, Gabr MT, Henning GM, Pigge FC, Schultz MK. Synthesis and Evaluation of Tetraarylethylene-based Mono-, Bis-, and Tris(pyridinium) Derivatives for Image-Guided Mitochondria-Specific Targeting and Cytotoxicity of Metastatic Melanoma Cells. Bioconjug Chem. 2016 Oct 19;27(10):2424-2430. Epub 2016 Sep 23.
Inventor Bio: Michael K. Schultz
https://medicine.uiowa.edu/internalmedicine/profile/michael-schultz
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Application pending
- Patent Link: http://www.flintbox.com/public/project/31453/
- Research Institute: University of Iowa
- Disease Focus: Melanoma
- Basis of Invention: Mitochondrial-targeted delivery vehicle for imaging and therapy
- How it works: Fluorescent lipophilic vinylpyridinium cations built from tetra-arylethylene scaffolds accumulate within melanoma mitochondria via targeting of the hyperpolarized membrane
- Lead Challenge Inventor: Michael Schultz
- Inventors: Michael Schultz, Christopher Pigge, Moustafa Gabr, Jessica Reedy
- Development Stage: in vitro
- Novelty: Specific drug targeting to the mitochondria and imaging of the delivery
- Clinical Applications: Drug delivery for melanoma treatment
General Description:
Prof. Schultz’s lab at the University of Iowa has developed a novel image guided therapy for cancer. This invention relates to a class of molecules, tetra-arylethylene derivatives, that can specifically deliver drugs to mitochondria in tumor cells. Data demonstrates that this platform can be designed to accumulate in the melanoma mitochondrial membranes, disrupt tumor cell metabolism, and induce cell death. In addition, this invention allows for imaging the accumulation of the delivery vehicle molecule in cells, a novel property of lipophilic cations.
Scientific Progress:
The data suggest that lipophilic−cationic and polycationic−heteroaromatic tetra-arylethylenes pass through the hydrophobic mitochondrial membrane lipid bilayer, move down the negative mitochondrial membrane voltage potential, and preferentially imbed in the hyperpolarized mitochondria membranes of melanoma cells. Imaging of the accumulation of the tetra-arylethylene-based compounds demonstrated melanoma-cell specific accumulation with little accumulation in normal human fibroblasts as controls. It was further found that vinylpyridine derivative accumulation in melanoma cells disrupts the cellular oxidation state and induces increased toxicity in melanoma cells relative to nonmalignant cells.
Future Directions:
- In vivo validation
Strengths:
- Kills cancer, specifically melanoma, cells
- Allows for precise visualization of therapeutic in cancer cell
- Better monitoring method
Patent Status:
Legal Status: Application pending
Publication PMID: 27902770, 27643916
Publications:
Schibler J, Tomanek-Chalkley AM, Reedy JL, Zhan F, Spitz DR, Schultz MK, Goel A. Mitochondrial-Targeted Decyl-Triphenylphosphonium Enhances 2-Deoxy-D-Glucose Mediated Oxidative Stress and Clonogenic Killing of Multiple Myeloma Cells. PLoS One. 2016 Nov 30;11(11):e0167323. doi: 10.1371/journal.pone.0167323. eCollection 2016.
Reedy JL, Hedlund DK, Gabr MT, Henning GM, Pigge FC, Schultz MK. Synthesis and Evaluation of Tetraarylethylene-based Mono-, Bis-, and Tris(pyridinium) Derivatives for Image-Guided Mitochondria-Specific Targeting and Cytotoxicity of Metastatic Melanoma Cells. Bioconjug Chem. 2016 Oct 19;27(10):2424-2430. Epub 2016 Sep 23.
Inventor Bio: Michael K. Schultz
https://medicine.uiowa.edu/internalmedicine/profile/michael-schultz
