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 language | English |
|---|---|
| Article number | 29018 |
| Journal | Scientific Reports |
| Volume | 6 |
| DOIs | |
| Publication status | Published - 2016 Jul 4 |
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Cite this
Programmed activation of cancer cell apoptosis : A tumor-targeted phototherapeutic topoisomerase I inhibitor. / Shin, Weon Sup; Han, Jiyou; Kumar, Rajesh; Lee, Gyung Gyu; Sessler, Jonathan L.; Kim, Jong-Hoon; Kim, Jong Seung.
In: Scientific Reports, Vol. 6, 29018, 04.07.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Programmed activation of cancer cell apoptosis
T2 - A tumor-targeted phototherapeutic topoisomerase I inhibitor
AU - Shin, Weon Sup
AU - Han, Jiyou
AU - Kumar, Rajesh
AU - Lee, Gyung Gyu
AU - Sessler, Jonathan L.
AU - Kim, Jong-Hoon
AU - Kim, Jong Seung
PY - 2016/7/4
Y1 - 2016/7/4
N2 - 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").
AB - 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").
UR - http://www.scopus.com/inward/record.url?scp=84977269769&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84977269769&partnerID=8YFLogxK
U2 - 10.1038/srep29018
DO - 10.1038/srep29018
M3 - Article
C2 - 27374023
AN - SCOPUS:84977269769
VL - 6
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 29018
ER -