Novel Fluorinated Porphyrins Sensitize Tumor Cells to Photodamage in Normoxia and Hypoxia: Synthesis and Biocompatible Formulations

Abstract

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.

High‐Contrast and Fast‐Removable 19F‐MRI Labels with Perfluoro‐tert‐Butyl Substituents

“…The balanced lipophilicity of these compounds will allow the introduction of dyes into emulsion particles, such as bodipy [24][25][26] or porphyrins [27] with perfluoroalkyl substituents as an additional marker or agent for photodynamic therapy. The study of the properties of the synthesized compounds as 19 F MRI contrast agents and their distribution in living systems will follow.…”

Perfluorocarbon Nanoemulsions with Fluorous Chlorin-Type Photosensitizers for Antitumor Photodynamic Therapy in Hypoxia

“…Preparation of benzaldehydes 1a-c was carried out by reaction of PFBA with corresponding polyfluoroaliphatic alcohols. In our previous report, this reaction was performed in dimethylformamide (DMF) in the presence of potassium fluoride at room temperature for 5-10 h [13]. We optimized the reaction conditions and the method of isolation of the final product.…”

“…Previously, we have reported the synthesis of porphyrins 2a and 2c [13,24]. Scheme 1 shows an improved synthetic approach.…”

“…Therefore, incorporation of a PS into PFCs emerges as a promising approach to eliminate tumor cells in hypoxia [6]. To this end, three PFC-based strategies have been developed to enhance PDT efficacy via improved oxygen delivery, including the following: (1) synthesis of PS-loaded PFC nanoparticles [7][8][9]; (2) fluorinated polymers to encapsulate PS [10][11][12]; and (3) PFC nanoparticles with fluorous PS [6,13]. The first approach is simple and requires no organic synthesis, as all materials are commercially available.…”

“…The second approach presumes the use of fluorinated polymers that act both as surfactants and a fluorous phase for PSs. The third approach [6,13] utilizes a PS modified with perfluorinated alkyl chains to minimize aggregation and place the PS in a closer proximity to oxygen-enriched PFCs. However, porphyrin-based PSs used in these studies absorb light in the UV-A region, therefore tissue photodamage is limited.…”