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Newly Synthesized Lipid–Porphyrin Conjugates: Evaluation of Their Self‐Assembling Properties, Their Miscibility with Phospholipids and Their Photodynamic Activity In Vitro
Author(s) -
Massiot Julien,
Rosilio Véronique,
Ibrahim Nada,
Yamamoto Akihisa,
Nicolas Valérie,
Konovalov Oleg,
Tanaka Motomu,
Makky Ali
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804865
Subject(s) - porphyrin , chemistry , photodynamic therapy , liposome , photosensitizer , vesicle , biophysics , conjugate , phototoxicity , in vitro , combinatorial chemistry , photochemistry , membrane , biochemistry , organic chemistry , biology , mathematics , mathematical analysis
Lipid–porphyrin conjugates are considered nowadays as promising building blocks for the conception of supramolecular structures with multifunctional properties, required for efficient cancer therapy by photodynamic therapy (PDT). The synthesis of two new lipid–porphyrin conjugates coupling pheophorbide‐a (Pheo‐a), a photosensitizer derived from chlorophyll‐a, to either chemically modified lyso‐phosphatidylcholine (PhLPC) or egg lyso‐sphingomyelin (PhLSM) is reported. The impact of the lipid backbone of these conjugates on their self‐assembling properties, as well as on their physicochemical properties, including interfacial behavior at the air/buffer interface, fluorescence and absorption properties, thermotropic behavior, and incorporation rate in the membrane of liposomes were studied. Finally, their photodynamic activity was evaluated on esophageal squamous cell carcinoma (ESCC) and normal esophageal squamous epithelium cell lines. The liposome‐like vesicles resulting from self‐assembly of the pure conjugates were unstable and turned into aggregates with undefined structure within few days. However, both lipid–porphyrin conjugates could be efficiently incorporated in lipid vesicles, with higher loading rates than unconjugated Pheo‐a. Interestingly, phototoxicity tests of free and liposome‐incorporated lipid–porphyrin conjugates demonstrated a better selectivity in vitro to esophageal squamous cell carcinoma relative to normal cells.