title: Comparison of intracellular accumulation and cytotoxicity of free mTHPC and mTHPC-loaded PLGA nanoparticles in human colon carcinoma cells.
abstract: The second generation photosensitizer mTHPC was approved by the European Medicines Agency (EMA) for the palliative treatment of advanced head and neck cancer in October 2001. It is known that mTHPC possesses a significant phototoxicity against a variety of human cancer cells in vitro but also exhibits dark toxicity and can cause adverse effects (especially skin photosensitization). Due to its poor water solubility, the administration of hydrophobic photosensitizer still presents several difficulties. To overcome the administration problems, the use of nanoparticles as drug carrier systems is much investigated. Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) have been extensively studied as delivery systems into tumours due to their biocompatibility and biodegradability. The goal of this study was the comparison of free mTHPC and mTHPC-loaded PLGA nanoparticles concerning cytotoxicity and intracellular accumulation in human colon carcinoma cells (HT29). The nanoparticles delivered the photosensitizer to the colon carcinoma cells and enabled drug release without losing its activity. The cytotoxicity assays showed a time- and concentration-dependent decrease in cell proliferation and viability after illumination. However, first and foremost mTHPC lost its dark toxic effects using the PLGA nanoparticles as a drug carrier system. Therefore, PLGA nanoparticles are a promising drug carrier system for the hydrophobic photosensitizer mTHPC.
authors.affiliation: Fraunhofer-Institute for Biomedical Engineering, D-66386 Straße Ingbert, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Löw
authors.forename: Thomas
authors.initials: T
authors.lastname: Knobloch
authors.forename: Sylvia
authors.initials: S
authors.lastname: Wagner
authors.forename: Arno
authors.initials: A
authors.lastname: Wiehe
authors.forename: Andrea
authors.initials: A
authors.lastname: Engel
authors.forename: Klaus
authors.initials: K
authors.lastname: Langer
authors.forename: Hagen
authors.initials: H
authors.lastname: von Briesen
mesh_terms: D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005434:Flow Cytometry; D019073:HT29 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D019344:Lactic Acid / Q000633:toxicity*; D008652:Mesoporphyrins / Q000633:toxicity*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000633:toxicity*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism
chemical_list: D008652:Mesoporphyrins; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C072269:temoporfin; D001973:Bromodeoxyuridine