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Light-activated Vitamin B12 Derivatives as Theranostic Agents (Conference Presentation)
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Paper Abstract

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.

Paper Details

Date Published: 4 March 2019
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Proc. SPIE 10862, Molecular-Guided Surgery: Molecules, Devices, and Applications V, 108620M (4 March 2019); doi: 10.1117/12.2515379
Show Author Affiliations
Jennifer R. Shell, Dartmouth College (United States)
Liberty N. Gendron, St. Anselm College (United States)
Dillon C. Zites, Norwich Univ. (United States)
Thomas A. Shell, Norwich Univ. (United States)
Brian W. Pogue, Dartmouth College (United States)


Published in SPIE Proceedings Vol. 10862:
Molecular-Guided Surgery: Molecules, Devices, and Applications V
Brian W. Pogue; Sylvain Gioux, Editor(s)

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