Mr. Colter G. Sheveland Profile

Colter G. Sheveland

at Norwich Univ.

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Proceedings Article | 14 August 2019 Presentation

Near infrared light-mediated delivery of anticancer agents (Conference Presentation)

Thomas Shell, Jennifer Shell, Colter Sheveland, Dillon Zites

Proceedings Volume 11070, 110703K (2019) https://doi.org/10.1117/12.2528271

KEYWORDS: Near infrared, Cancer, Ultraviolet radiation, Tissue optics, Molecules, Oncology, Molecular biology, Tissues

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Light-responsive compounds can be utilized to control spatially and temporally the initiation of biochemical processes. This has the potential to improve the treatment of diseases, such as cancers, by controlling the location of drug activity at the site of disease rather than the drug acting systemically. This would reduce side-effects as well as the overall systemic dose of anticancer agents. Until recently light-responsive molecules that released active compounds in a stoichiometric manner required the use of short wavelength, high energy ultraviolet light (UV). These compounds cannot be used to treat disease because the required light wavelengths are readily absorbed by biological molecules preventing the light from penetrating tissue to an appreciable extent. Recently, we have a developed a platform technology that combines Vitamin B12 and a near infrared (NIR) absorbing fluorophore that converts an inactivated drug into an active form when exposed to NIR. In contrast to UV, NIR is poorly absorbed by biological tissues. Therefore, NIR penetrates tissue and can be used for photochemotherapeutic treatment of disease. In addition to targeting diseased tissue based on controlling drug activity by regulating light exposure, these compounds target cancer cells due to the Vitamin B12 moiety because rapidly dividing cancer cells have an increased demand for Vitamin B12 in comparison to normal, healthy cells. The reported technology could improve treatment of certain by diseases by affording effective treatment while reducing side effects.

Proceedings Article | 14 August 2019 Presentation

Tumor targeting vitamin B12 derivatives for x-ray activated chemotherapy (Conference Presentation)

Jennifer Shell, Thomas Shell, Brian Pogue, Liberty Gendron, Colter Sheveland

Proceedings Volume 11070, 110705G (2019) https://doi.org/10.1117/12.2528263

KEYWORDS: Tumors, X-rays, Cancer, Radiotherapy, Receptors, Tissues

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X-Ray activated pharmaceutical therapy is highly sought after as it provides deep tissue, synergistic method of treating cancers in which the standard method of care involves radiotherapy. Traditional drugs utilized as neoadjuvant chemotherapy have significant side effects and a lack of selectivity, leaving a dire need for targeted drug delivery methods. We have recently developed a unique delivery platform whereby the drug is conjugated to an alkylcobalamin vitamin B12 scaffold, and these alkylcobalamins are actively transported into cells by transcobalamin receptors (TCblR). A large number of cancer types have enhanced expression of these receptors; therefore, the drug-cobalamin conjugate could be effectively ferried into the tumor selectively via the TCblR pathway. This delivery system provides light-activatable release of chemotherapeutics. Due to the drug becoming active at the specific site that it is needed, such as a tumor, the potential side effects of that drug in organs at risk are mitigated. As a proof of concept, we have found that a fluorescent cobalamin derivative localized within xenograft tumors in mice, demonstrating the effectiveness of the vitamin B12 scaffold as a theranostic targeting agent. In addition, this derivative is also activated with clinical X-ray doses from a linear accelerator. We explored the ability of a variety of cobalamin drug conjugates to be used in combination with radiotherapy to elicit an enhanced reduction in tumor margins in pancreatic adenocarcinoma models.

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