Mechanisms of porphyrinoid localization in tumors

Abstract

The photosensitizing and pharmacokinetic properties of porphyrin-type compounds have been investigated for nearly a century. In the last decade, two porphyrin derivatives were approved in the U.S.A. and in several other countries for the photodynamic treatment of various lesions. An overview of the different mechanisms for preferential porphyrinoid localization in malignant tumors is presented herein. Several uptake pathways are possible for each photosensitizer, which are determined by its structure, mode of delivery and tumor type. Comparisons of the different mechanisms and correlations with the structure of the sensitizer are presented. Current delivery systems for porphyrin sensitizers are described, as well as recent strategies for enhancing their tumor-specificity, including conjugation to a carrier system that selectively targets a tumor-associated receptor or antigen.

Chiral porphyrazine near-IR optical imaging agent exhibiting preferential tumor accumulation

“…Hydrophobic tetrapyrroles accumulate in cells through a variety of mechanisms, including passive diffusion, entry by flipping through the membrane, and association with serum proteins (11,26). Serum components, including albumin and LDL, have been shown to act as delivery vehicles for hydrophobic compounds through receptordependent and independent endocytosis, both leading to lysosomal accumulation (26)(27)(28).…”

“…Heteroatom-functionalized pzs have intense NIR absorption/emission (8) and recently have been considered as optical contrast agents for tumor detection and as a platform for cancer treatment using PDT (9,10). These pzs are synthetically flexible (8), making it possible to independently fine tune their NIR optical characteristics and amphiphilicity, a characteristic shown to dictate tumor retention of porphyrinoids (11,12).…”

Erythrocytes Membrane Photodestruction Sensitized Chlorophyll a Derivatives: Some Structure-Activity Regularities

“…methyl-13(1)-desoxopyropheophorbide a (15) [55] were obtained according to literature procedures. Methyl-13(1)-hydroxy-13(1)desoxo-pheophorbide a (18), [57] chlorin e 6 13(1)-N-(2-hydroxyethyl)amide-15(3),17(3)-dimethyl ester (24), [58] chlorin e 6 13(1)-morpholinylamide-15(3),17(3)-dimethyl ester (25), [58] rodin g 7 13(1)-N,N-dimethylamide-15(3),17(3)-dimethyl ester (34), [59] chlorin e 6 13(1),17(3)-N,N'-(2-hydroxyethyl)diamide-15(3),17(3)-dimethyl ester (32), [60] and chlorin e 6 13(1),15(2),17(3)-N,N',N''-(2-hydroxyethyl)triamide (33) [60] were also obtained according to the known procedures.…”

“…[1][2][3][4][5][6] Thus, new PS searching among chlorophyll a derivatives is of a good chance and the investigation of their activity mechanisms and "structure-activity" regularities are of a great interest for new potential PS synthesis planning. [15,21,[28][29][30][31][32] Variation of chlorins chemical structure features such as charge, hydrophobicity and steric properties leads to the significant changing of the pigments ability to insert into the cell which can define their photodynamic effectivity. [33,34] The ability of pigments to interact with membrane structures is of a great significance for photosensitizing activity appearance in cell culture and in vivo.…”

Chlorin p6 Cycloimides: Syntheses, Properties and Possible Fields of Application

“…Дан-ные по химии и фотодинамической активности этих соединений, а также их многочисленных производных подробно рассмотрены в монографиях [1][2][3] и обзорных статьях. [4][5][6][7][8][9][10][11][12] На основе хлорина e 6 созданы препараты второго поколения Фотодитазин (Россия), Радахлорин (Россия), Фотолон (Республика Беларусь), моно-L-аспартилхлорин (Япония). В США в настоящее время проходит клинические испытания 3-(1´-гексилокси) этилпирофеофорбид a (HPPH).…”