Targeting of the photocytotoxic compound AlPcS4 to Hela cells by transferrin conjugated PEG-liposomes - PubMed (original) (raw)

. 2002 Sep 1;101(1):78-85.

doi: 10.1002/ijc.10548.

Affiliations

• PMID: 12209592
• DOI: 10.1002/ijc.10548

Targeting of the photocytotoxic compound AlPcS4 to Hela cells by transferrin conjugated PEG-liposomes

Antoon Gijsens et al. Int J Cancer. 2002.

Abstract

Photodynamic therapy has attracted increasing interest over the last few years, whereby the activation of photosensitizers by light causes the production of reactive oxygen species (ROS), such as singlet oxygen, which are cytotoxic. The goal of our study was to enhance the photodynamic activity of the photosensitizer aluminum phthalocyanine tetrasulfonate (AlPcS4) through its specific delivery to tumor cells. Since many tumor cells, among which are HeLa cells, overexpress the transferrin receptor, we synthesized transferrin conjugated PEG-liposomes that contained AlPcS4 that could be internalized by receptor mediated endocytosis. The antiproliferative activity of the targeted liposomes was evaluated and compared to the native AlPcS4 and the non-targeted liposome. These findings were supplemented with data on intracellular concentration of the photo-active compounds. The accumulation together with ROS production after irradiation was visualized by using confocal microscopy to confirm the data found in the antiproliferative and accumulation assay. Tf-Lip-AlPcS4 was 10 times more photocytotoxic (IC(50), 0.63 microM) than free AlPcS4 at a light dose of 45 kJ/m whereas Lip-AlPcS4 displayed no photocytotoxicity at all. The high photocytotoxicity of Tf-Lip-AlPcS4 was shown to be the result of a high intracellular concentration (136.5 microM) in HeLa cells, which could be lowered dramatically by incubating the conjugate with a competing transferrin concentration. The images of intracellular accumulation and ROS production matched the accumulation and photocytotoxicity profile of the different photo-active compounds. The photodynamic activity of the Tf-Lip-AlPcS4 conjugate on HeLa cells is much more potent than free AlPcS4 as a result of selective transferrin receptor mediated uptake.

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