Photodynamic therapy (PDT) is an emerging cancer treatment approach that uses light in combination with a photosensitizing agent (PS) to trigger the production of DNA damaging reactive oxygen species (ROS) in a spatially and temporally controlled fashion. Strong absorption by the PS within the near-infrared (NIR) wavelength region is preferred due to minimal absorption of light in this range by biological tissues. This allows deeper penetration of incident irradiation and more efficient activation of PDT photosensitizing agents. Due to their ability to strongly absorb NIR light, cyanine dyes have recently been studied in PDT. Damage to mitochondrial DNA is often preferred as it can induce the destruction of targeted cells by apoptosis rather than tissue-damaging necrosis. We have previously reported that a brominated 4-quinolinium pentamethylene carbocyanine dye containing a mitochondrial-targeting triphenyl phosphonium unit induces efficient DNA cleavage in the NIR wavelength range. Given this, in the present study, we describe optimized NIR DNA cleavage by two new derivatives of this dye that instead of bromine respectively contain a hydrogen or a chlorine atom at the <i>meso </i>position of the dyes’ pentamethylene bridge. Photocleavage reactions were performed by irradiating pH 7.0 buffered solutions containing 38 microM bp of pUC19 DNA and dye concentrations ranging from 0 to 20 microM at 808, 830, or 850 nm across different time intervals. Our optimized results point to strong photocleavage of DNA by the new dyes in the near-IR wavelength range.

Optimized near-IR DNA photocleavage by carbocyanine dyes containing a mitochondrial-targeting triphenyl phosphonium moiety

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.