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Title 

Enhanced photodynamic cancer treatment by mitochondria-targeting and brominated near-infrared fluorophores

Authors 

I NohD Y LeeH KimC U JeongY LeeJungoh AhnH HyunJ H ParkY C Kim

Publisher 

Wiley Open Access

Issue Date 

2018

Citation 

Advanced Science

Keywords 

cancer therapyheptamethine cyanine dyemitochondria targetingnear-infrared (NIR) dyephotodynamic therapy

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

ISSN 

2198-3844

Link 

http://dx.doi.org/10.1002/advs.201700481

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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