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”).
Highlights
Number of chemical and biological contexts[13,14,15,16,17]
The synthesis of phototherapeutic agent 1 (PT-1) is shown in Fig. 1a. 2-Azidoethanol 2 and compound 4 were synthesized by previously reported methods[25,26]
To validate and compare the mode of action of PT-1 and SN-38, we examined the expression of topoisomerase I and various genes, including mitochondrial apoptotic genes, genes associated with cell death receptors, caspase enzymes, and a multidrug resistance (MDR) protein involved in the apoptosis of cancer cells (Fig. 3e)
Summary
Number of chemical and biological contexts[13,14,15,16,17]. light-sensitive nanoparticles, such as polymeric up-conversion nanoparticles have been utilized in various practical applications[18,19,20,21]. In the case of cancer treatment, the use of a light-activated prodrug may allow for more precise control of drug release at the tumor site, along with the potential for both modulating the therapeutic activity. The use of light-activated compounds for cancer drug release and the concurrent monitoring of targeted drug delivery has not been explored. We have constructed a tumor-targeting masked phototherapeutic agent 1 (PT-1) that contains 7-ethyl-10-hydroxycamptothecin (SN-38)—a prodrug of irinotecan—and nitrovanillin as a phototriggered moiety (Fig. 1a). In vitro and in vivo studies reveal significant inhibition of cancer growth by PT-1 upon irradiation with 405 nm laser light
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
