Photocytotoxic action of EGF-PVA-Sn(IV)chlorin e6 and EGF-dextran-Sn(IV)chlorin e6 internalizable conjugates on A431 cells. 1998

A Gijsens, and P De Witte
Laboratorium voor Farmaceutische Biologie en Fytofarmacologie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium.

Certain tumour cells, such as squamous carcinoma cells, express an increased number of epidermal growth factor (EGF) receptors. The goal of this study was the targeted delivery of Sn(IV)chlorin e6 (SnCe6) to tumours that overexpress the EGF receptor. Therefore EGF was conjugated to the photosensitizer through a carrier, such as dextran (Dex) and polyvinylalcohol (PVA). These conjugates were then compared to a conjugate of the photosensitizer to dextran or PVA alone. The EGF-Dex-SnCe6 conjugates bound specifically to the EGF receptors of the human squamous carcinoma cell line A431 in contrast to EGF-PVA-SnCe6. However, EGF-PVA-SnCe6 exhibited a higher photocytotoxicity (CC50, 2.8 microM) than EGF-Dex-SnCe6 (CC50, >10 microM) and SnCe6 (CC50, >10 microM). PVA-SnCe6 had a similar photocytotoxicity (CC50, 3.5 microM) to EGF-PVA-SnCe6, indicating that PVA, more than EGF, plays a determinant role in the uptake of the conjugates by A431 cells. Together with the improved affinity of EGF-Dex-SnCe6 over EGF-PVA-SnCe6 for the EGF receptor, the former displayed a small increased photocytotoxicity over Dex-SnCe6, reflecting a limited EGF receptor mediated uptake effect. It was concluded that the photodynamic activity of the EGF-conjugate turns out to be strongly dependent on the carrier used.

UI MeSH Term Description Entries
D008027 Light That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range. Light, Visible,Photoradiation,Radiation, Visible,Visible Radiation,Photoradiations,Radiations, Visible,Visible Light,Visible Radiations
D008665 Metalloporphyrins Porphyrins which are combined with a metal ion. The metal is bound equally to all four nitrogen atoms of the pyrrole rings. They possess characteristic absorption spectra which can be utilized for identification or quantitative estimation of porphyrins and porphyrin-bound compounds. Metalloporphyrin
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D003911 Dextrans A group of glucose polymers made by certain bacteria. Dextrans are used therapeutically as plasma volume expanders and anticoagulants. They are also commonly used in biological experimentation and in industry for a wide variety of purposes. Dextran,Dextran 40,Dextran 40000,Dextran 70,Dextran 75,Dextran 80,Dextran B-1355,Dextran B-1355-S,Dextran B1355,Dextran B512,Dextran Derivatives,Dextran M 70,Dextran T 70,Dextran T-40,Dextran T-500,Hemodex,Hyskon,Infukoll,Macrodex,Polyglucin,Promit,Rheodextran,Rheoisodex,Rheomacrodex,Rheopolyglucin,Rondex,Saviosol,Dextran B 1355,Dextran B 1355 S,Dextran T 40,Dextran T 500
D004337 Drug Carriers Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. Drug Carrier
D004815 Epidermal Growth Factor A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form. EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013347 Subcellular Fractions Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163) Fraction, Subcellular,Fractions, Subcellular,Subcellular Fraction

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