Abstract
Mesotetra(4-carboxyphenyl)porphyrin (mTCPP) is a commercially available small molecule fluorophore and photosensitizer with four free carboxylic acid groups. mTCPP can readily be conjugated with amines for facile attachment of functional groups. In this work, we synthesized and assessed tetravalent, lysine-conjugated mTCPP, for its potential applications in targeted imaging and photodynamic therapy. Fmoc-protected d-lysine or l-lysine was conjugated to mTCPP via amide coupling with the epsilon amine group of lysine, followed by Fmoc deprotection. The resulting compounds did not dissolve well in aqueous solvent, but could be solubilized with the assistance of surfactants, including cholic acid. The l-amino acid transporter (LAT1) can uptake diverse neutral l-amino acids. In vitro studies with U87 cells revealed a non-specific uptake of the hydrophobic Fmoc-protected lysine-conjugated mTCPP precursors, but not d- or l-lysine mTCPP. Likewise, only the Fmoc-protected compounds induced substantial phototoxicty in cells following incubation and irradiation with blue light. These experimental results do not provide evidence to suggest that lysine-mTCPP is able to specifically target cancer cells. However, they do highlight mTCPP as a convenient and accessible framework for assessing molecular targeting of photosensitizers.
Highlights
Photodynamic therapy (PDT) has been demonstrated as a minimally invasive ablative modality for cancer treatment [1,2]
When the compounds were irradiated with a 405 nm light source, both complexes showed time-dependent generation of singlet oxygen (Figure S6). These results demonstrate the potential photosensitization of the synthesized complexes and potential for PDT
The resulting porphyrin conjugates could be dispersed in various surfactants including 1% cholic acid
Summary
Photodynamic therapy (PDT) has been demonstrated as a minimally invasive ablative modality for cancer treatment [1,2]. Merits associated with PDT include low systemic toxicity, the ability to treat only light-targeted areas, and the possibility of undergoing repeated treatments without the development of resistance [3]. (i) a photosensitizer (PS) with a capacity to generate reactive oxygen species; (ii) light irradiation of the appropriate wavelength; and (iii) availability of oxygen in the target region [4]. Many photosensitizers have been described, porphyrin-based ones have been the most commonly used in the clinic [5,6]. Hematoporphyrin derivative (Photofrin), an oligomeric porphyrin mixture, was the first photosensitizer used in modern clinical practice of PDT for anti-tumor treatment, and has been used extensively [7,8,9,10]. Fluorescence imaging with PDT opens up intriguing possibilities, including image-guided therapies and feedback-driven light dosimetry [15]
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