Assessing Photosensitizer Targeting Using Meso-Tetra(Carboxyphenyl) Porphyrin

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.

An update in clinical utilization of photodynamic therapy for lung cancer

“…The choice of optimal combinations of photosensitizers, light sources, and treatment parameters are crucial for effective PDT [42,43]. The type of photosensitizer used, oxygen concentration within target tumor cells, a dose of light applied, and concentration of photosensitizer uptaken by cancer cells determine the cancer treatment efficacy of PDT [44][45][46][47]. PDT components can directly induce cellular damage to organelles and cell membranes, depending on where they are generated [21,22].…”

Metalloporphyrins in Medicine: From History to Recent Trends

“…Chitgupi and colleagues synthesized l -lysine modified with meso -tetra­(4-carboxyphenyl)­porphyrin, specifically internalized by U87 cells and without substantial phototoxicty. The derivative may be used in direct labeling of molecules or even fused with primary amino acid chain of protein, which allows synthesis of controlled targeted molecular probes . Pandey and coauthors reported on simple, fast, and stable system based on PLA and PLA-alginate particles loaded with NIR fluorophore–PtP for oxygen and glucose monitoring in patients.…”

Анизотропия И Спектроскопические Свойства Комплексов Молекул Мезо-Тетра(4-Карбоксифенил)порфирина С Алмазными Наночастицами

“…Известно, что порфирины могут использоваться как активные фотоагенты в различных оптических технологиях, в частности, в качестве фотосенсибилизаторов для целей фотодинамической терапии (ФДТ). В этой связи особое внимание привлекают порфирины с гидрофильными боковыми группами, так как они имеют высокую растворимость в водных растворах [1,2]. Однако молекулы порфиринов благодаря наличию заряженных групп в зависимости от окружения способны к различным реакциям агрегации, образованию димеров, олигомеров и т. д.…”