Title:Novel Fluorinated Porphyrins Sensitize Tumor Cells to Photodamage in Normoxia and Hypoxia: Synthesis and Biocompatible Formulations
VOLUME: 18 ISSUE: 4
Author(s):Elizaveta V. Belyaeva*, Alina A. Markova, Dmitry N. Kaluzhny, Andrei L. Sigan, Lev L. Gervitz, Aida N. Ataeva, Nikolai D. Chkanikov and Alexander A. Shtil
Affiliation:A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Moscow State University, Moscow, A.N.Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, Moscow, Blokhin National Medical Research Center of Oncology, Moscow
Keywords:Porphyrins, fluorine, perfluorocarbon, emulsions, photosensitizers, reactive oxygen species, hypoxia, tumor cells, cell death.
Abstract:Background: Hypoxia renders tumor cells refractory to treatment. One way to overcome this problem
is the design of drug delivery systems that contain the antitumor agent within an oxygen supply medium.
Objective: to evaluate whether the perfluorocarbon liquids (capable of retaining up to 50% v/v amounts of
O2 gas) can be tools for delivery of photosensitizers to hypoxic tumors.
Method: We synthesized a series of compounds in which fluoroaliphatic or fluoroaromatic moieties were
conjugated to the porphyrin ring in meso-positions. Two derivatives were tested as the solutions prepared
either from a dimethylformamide stock (‘free’ formulation) or from a perfluorocarbon emulsion in which the
photosensitizer is entrapped in the oxygenated medium.
Results: In the emulsion the hydrophobic photosensitizer and the gas transporting liquid represented a biocompatible
composition. Free formulations or perfluorocarbon emulsions of fluorinated porphyrins evoked little-to-null
dark cytotoxicity. In contrast, each formulation triggered cell death upon light activation. Photodamage in the presence
of fluorinated porphyrins was achievable not only at normoxic (20.9% O2 v/v) conditions but also in hypoxia
(0.5% O2). With new compounds dissolved in the medium the cell photodamage in hypoxia was negligible whereas
a significant photodamage was achieved with the emulsions of fluorinated porphyrins. The derivative with the
fluoroalkyl substituent was more potent than its structurally close analog carrying the fluoroaryl moiety.
Conclusion: Our new fluorinated porphyrin derivatives, especially their emulsions in which the photosensitizer
and the oxygenated medium are coupled into one phase, can be perspective for photoelimination of hypoxic
tumor cells.