Enhanced Photodynamic Cancer Treatment by Mitochondria‐Targeting and Brominated Near‐Infrared Fluorophores. Issue 3 (19th December 2017)

• Record Type: Journal Article
• Authors: Noh, Ilkoo; Lee, DaeYong; Kim, Heegon; Jeong, Chan‐Uk; Lee, Yunsoo; Ahn, Jung‐Oh; Hyun, Hoon; Park, Ji‐Ho; Kim, Yeu‐Chun
• Is Part Of: Advanced science. Volume 5:Issue 3(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-12-19
• Subjects: cancer therapy -- heptamethine cyanine dye -- mitochondria targeting -- near‐infrared (NIR) dye -- photodynamic therapy; Science -- Periodicals; 505
• DOI: 10.1002/advs.201700481
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: A noninvasive and selective therapy, photodynamic therapy (PDT) is widely researched in clinical fields; however, the lower efficiency of PDT can induce unexpected side effects. Mitochondria are extensively researched as target sites to maximize PDT effects because they play crucial roles in metabolism and can be used as cancer markers due to their high transmembrane potential. Here, a mitochondria targeting photodynamic therapeutic agent (MitDt) is developed. This photosensitizer is synthesized from heptamethine cyanine dyes, which are conjugated or modified as follows. The heptamethine meso‐position is conjugated with a triphenylphosphonium derivative for mitochondrial targeting, the N ‐alkyl side chain is modified for regulation of charge balance and solubility, and the indolenine groups are brominated to enhance reactive oxygen species generation (ROS) after laser irradiation. The synthesized MitDt increases the cancer uptake efficiency due to the lipo‐cationic properties of the triphenylphosphonium, and the PDT effects of MitDt are amplified after laser irradiation because mitochondria are susceptible to ROS, the response to which triggers an apoptotic anticancer effect. Consequently, these hypotheses are demonstrated by in vitro and in vivo studies, and the results indicate strong potential for use of MitDts as efficient single‐molecule‐based PDT agents for cancer treatment. Abstract : Mitochondria targeting photodynamic therapeutic agents (MitDt) including triphenylphosphonium, which can be guided to mitochondrial membranes, are devised. Among them, the brominated indolenine structure can boost reactive oxygen species production after near‐infrared (NIR) laser irradiation, which elicits outstanding cellular apoptotic death in vitro and in vivo. Therefore, MitDt suggests a promising therapeutic probe for cancer therapy.