Programmed activation of cancer cell apoptosis: A tumor-targeted phototherapeutic topoisomerase I inhibitor

Weon Sup Shin, Jiyou Han, Rajesh Kumar, Gyung Gyu Lee, Jonathan L. Sessler, Jong-Hoon Kim, Jong Seung Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We report here a tumor-targeting masked phototherapeutic agent 1 (PT-1). This system contains SN-38 - a prodrug of the topoisomerase I inhibitor irinotecan. Topoisomerase I is a vital enzyme that controls DNA topology during replication, transcription, and recombination. An elevated level of topoisomerase I is found in many carcinomas, making it an attractive target for the development of effective anticancer drugs. In addition, PT-1 contains both a photo-triggered moiety (nitrovanillin) and a cancer targeting unit (biotin). Upon light activation in cancer cells, PT-1 interferes with DNA re-ligation, diminishes the expression of topoisomerase I, and enhances the expression of inter alia mitochondrial apoptotic genes, death receptors, and caspase enzymes, inducing DNA damage and eventually leading to apoptosis. In vitro and in vivo studies showed significant inhibition of cancer growth and the hybrid system PT-1 thus shows promise as a programmed photo-therapeutic ("phototheranostic").

Original languageEnglish
Article number29018
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 2016 Jul 4

ASJC Scopus subject areas

  • General

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