Localized in vivo activation of a photoactivatable doxorubicin prodrug in deep tumor tissue

Stuart Ibsen, Eran Zahavy, Wolf Wrasidlo, Tomoko Hayashi, John Norton, Yongxuan Su, Stephen Adams, Sadik Esener

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Sparing sensitive healthy tissue from chemotherapy exposure is a critical challenge in the treatment of cancer. The work described here demonstrates the localized in vivo photoactivation of a new chemotherapy prodrug of doxorubicin (DOX). The DOX prodrug (DOX-PCB) was 200 times less toxic than DOX and was designed to release pure DOX when exposed to 365 nm light. This wavelength was chosen because it had good tissue penetration through a 1 cm diameter tumor, but had very low skin penetration, due to melanin absorption, preventing uncontrolled activation from outside sources. The light was delivered specifically to the tumor tissue using a specialized fiber-optic LED system. Pharmacokinetic studies showed that DOX-PCB had an α circulation half-life of 10 min which was comparable to that of DOX at 20 min. DOX-PCB demonstrated resistance to metabolic cleavage ensuring that exposure to 365 nm light was the main mode of in vivo activation. Tissue extractions from tumors exposed to 365 nm light in vivo showed the presence of DOX-PCB as well as activated DOX. The exposed tumors had six times more DOX concentration than nearby unexposed control tumors. This in vivo proof of concept demonstrates the first preferential activation of a photocleavable prodrug in deep tumor tissue.

Original languageEnglish (US)
Pages (from-to)698-708
Number of pages11
JournalPhotochemistry and Photobiology
Volume89
Issue number3
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Prodrugs
Doxorubicin
Tumors
polychlorinated biphenyls
tumors
Chemical activation
activation
Tissue
Neoplasms
Polychlorinated Biphenyls
chemotherapy
penetration
Light
melanin
Chemotherapy
half life
cleavage
fiber optics
light emitting diodes
cancer

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Biochemistry
  • Medicine(all)

Cite this

Localized in vivo activation of a photoactivatable doxorubicin prodrug in deep tumor tissue. / Ibsen, Stuart; Zahavy, Eran; Wrasidlo, Wolf; Hayashi, Tomoko; Norton, John; Su, Yongxuan; Adams, Stephen; Esener, Sadik.

In: Photochemistry and Photobiology, Vol. 89, No. 3, 05.2013, p. 698-708.

Research output: Contribution to journalArticle

Ibsen, Stuart ; Zahavy, Eran ; Wrasidlo, Wolf ; Hayashi, Tomoko ; Norton, John ; Su, Yongxuan ; Adams, Stephen ; Esener, Sadik. / Localized in vivo activation of a photoactivatable doxorubicin prodrug in deep tumor tissue. In: Photochemistry and Photobiology. 2013 ; Vol. 89, No. 3. pp. 698-708.
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