Spectroelectrochemical and ESR investigation of free radicals derived from indotricarbocyanine dyes for photodynamic therapy

Abstract

Photodynamic therapy (PDT) is a promising and minimally invasive therapeutic method for the treatment of various types of cancer [1–4]. Besides the direct destruction of tumor cells, PDT causes robust antitumor immune responses improving the overall effectiveness of the treatment [5–8]. An essential component of PDT is a photosensitizer (PS), i.e., a chemical compound that intensely accumulates in tumor cells and induces cytotoxicity upon photoactivation. The phototherapeutic window, where biological tissues exhibit maximum transparency, is between 750 and 900 nm [9]. However, many PSs have absorption bands in the 600–700 nm range [2,4,5], which limits the penetration depth of the excitation light into a tumor. Developing PSs with improved properties remains a very important task. Cyanine dyes have great potential to be used in PDT due to their intense light absorption in the near-infrared (NIR) spectral range, excellent fluorescent characteristics, and low dark toxicity [9–17]. Cyanine dyes provide substantial penetration depth of the excitation light into biological tissues. Another advantage is the tendency of cationic cyanine dyes to accumulate in mitochondria [18] since mitochondria-targeted PDT was found to be particularly effective [11,12]. It is generally accepted that cytotoxicity in PDT is due to the generation of reactive oxygen species [2,4]. As a result, PSs can lose efficiency under hypoxic conditions [16]. Interestingly, cationic indotricarbocyanine dyes with bromide counterion were found to retain photodynamic activity even under hypoxia [19]. In this work, we investigate a cationic indotricarbocyanine dye that has demonstrated high photodynamic activity in vivo [20]. PDT with this dye produced an impressive 2.5 cm deep necrotic lesion. The dye was photoactivated at 780 nm, which provided the advantage of the high transparency of biological tissues [21]. Poor water solubility often limits biomedical applications of cyanine dyes [11,16]. Water solubility, biocompatibility, and tumor-to-nontumor specificity of the dye under study were improved by covalent linking of polyethylene glycol substituents to the dy molecules [20].