期刊
PHOTOCHEMISTRY AND PHOTOBIOLOGY
卷 89, 期 3, 页码 698-708出版社
WILEY
DOI: 10.1111/php.12045
关键词
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资金
- National Cancer Institute [5 U54 CA119335]
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 365nm light. This wavelength was chosen because it had good tissue penetration through a 1cm 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 circulation half-life of 10min which was comparable to that of DOX at 20min. DOX-PCB demonstrated resistance to metabolic cleavage ensuring that exposure to 365nm light was the main mode of in vivo activation. Tissue extractions from tumors exposed to 365nm 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.
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