Recent Progress in Chemical Modifications of Chlorophylls and Bacteriochlorophylls for the Applications in Photodynamic Therapy.
Since photodynamic therapy emerged as a promising cancer treatment, the development of photosensitizers has gained great interest. In this context, the photosynthetic pigments, chlorophylls and bacteriochlorophylls, as excellent natural photosensitizers, attracted much attention. In effect, several (bacterio) chlorophyll-based phototherapeutic agents have been developed and (or are about to) enter the clinics. The aim of this review article is to give a survey of the advances in the synthetic chemistry of these pigments which have been made over the last decade, and which are pertinent to the application of their derivatives as photosensitizers for photodynamic therapy (PDT). The review focuses on the synthetic strategies undertaken to obtain novel derivatives of (bacterio)chlorophylls with both enhanced photosensitizing and tumorlocalizing properties, and also improved photo- and chemical stability. These include modifications of the C- 17-ester moiety, the isocyclic ring, the central binding pocket, and the derivatization of peripheral functionalities at the C-3 and C-7 positions with carbohydrate-, peptide-, and nanoparticle moieties or other residues. The effects of these modifications on essential features of the pigments are discussed, such as the efficiency of reactive oxygen species generation, photostability, phototoxicity and interactions with living organisms. The review is divided into several sections. In the first part, the principles of PDT and photosensitizer action are briefly described. Then the relevant photophysical features of (bacterio)chlorophylls and earlier approaches to their modification are summarized. Next, a more detailed overview of the progress in synthetic methods is given, followed by a discussion of the effects of these modifications on the photophysics of the pigments and on their biological activity.
Jakub
J
Staron
Bożena
B
Boron
Dariusz
D
Karcz
Małgorzata
M
Szczygieł
Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland. leszek.fiedor@uj.edu.pl.
Leszek
L
Fiedor
D000818:Animals; D001429:Bacteriochlorophylls / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002734:Chlorophyll / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; D002734:Chlorophyll