Light-activated Vitamin B12 Derivatives as Theranostic Agents (Conference Presentation)
| Autor: | Jennifer R. Shell, Dillon C. Zites, Brian W. Pogue, Thomas A. Shell, Liberty N. Gendron |
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| Rok vydání: | 2019 |
| Předmět: |
Drug
Chemistry media_common.quotation_subject Cell nutritional and metabolic diseases medicine.disease Cobalamin chemistry.chemical_compound medicine.anatomical_structure In vivo hemic and lymphatic diseases Pancreatic cancer Drug delivery polycyclic compounds medicine Cancer research heterocyclic compounds Erlotinib Vitamin B12 medicine.drug media_common |
| Zdroj: | Molecular-Guided Surgery: Molecules, Devices, and Applications V. |
| Popis: | The discovery of new tumor targeting agents is desirable to expand imaging and drug delivery platforms. Cobalamins, vitamin B12 derivatives, selectively accumulate in tumor versus benign tissue due to overexpression of transcobalamin receptors in a variety of cancer types. Multiple forms of this vitamin are taken into cells via transport through transcobalamin receptors on the cell surface. Alkylcobalamins are light-activatable, and we have discovered that the wavelength of this light activation is tunable via appendage of a fluorophore. We have been able to harness this cobalamin platform to release drugs with a variety of wavelengths of light, including those within the optical window of tissue. This cobalamin drug delivery platform provides selective spatiotemporal activation of drug only where needed, thereby diminishing side effects of traditional chemotherapy. A Bodipy650-cobalamin was synthesized and utilized to study the tumor targeting ability of cobalamin derivatives in athymic nude mice with subcutaneous MCF-7 and MIA PaCa-2 tumors, which have been demonstrated to overexpress transcobalamin receptors. The fluorescently labeled cobalamin was injected intravenously into the mice and allowed to incubate for a series of time points. Fluorescence imaging revealed that this cobalamin conjugate selectively accumulated in both tumor types. We utilized this cobalamin platform for tumor selective, light-activated delivery of the pancreatic cancer drugs erlotinib and SN38. We determined light-induced apoptosis in MIA PaCa-2 cells in vitro and explored the reduction of MIA PaCa-2 tumors in vivo utilizing these cobalamin drug conjugates. This cobalamin platform provides potential for development of new theranostic tools for drug delivery. |
| Databáze: | OpenAIRE |
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