title: Do folate-receptor targeted liposomal photosensitizers enhance photodynamic therapy selectivity?
abstract: One of the current goals in photodynamic therapy research is to enhance the selective targeting of tumor cells in order to minimize the risk and the extension of unwanted side-effects caused by normal cell damage. Special attention is given to receptor mediated delivery systems, in particular, to those targeted to folate receptor. Incorporation of a model photosensitizer (ZnTPP) into a folate-targeted liposomal formulation has been shown to lead an uptake by HeLa cells (folate receptor positive cells) 2-fold higher than the non-targeted formulation. As a result, the photocytotoxicity induced by folate-targeted liposomes was improved. This selectivity was completely inhibited with an excess of folic acid present in the cell culture media. Moreover, A549 cells (folate receptor deficient cells) have not shown variations in the liposomal incorporation. Nevertheless, the differences observed were slighter than expected. Both folate-targeted and non-targeted liposomes localize in acidic lysosomes, which confirms that the non-specific adsorptive pathway is also involved. These results are consistent with the singlet oxygen kinetics measured in living cells treated with both liposomal formulations.
authors.affiliation: Institut Químic de Sarrià, Universitat Ramon Llull, Vía Augusta 390, 08017 Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Díaz
authors.forename: Santi
authors.initials: S
authors.lastname: Nonell
authors.forename: Angeles
authors.initials: A
authors.lastname: Villanueva
authors.forename: Juan C
authors.initials: JC
authors.lastname: Stockert
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cañete
authors.forename: Ana
authors.initials: A
authors.lastname: Casadó
authors.forename: Margarita
authors.initials: M
authors.lastname: Mora
authors.forename: M Lluïsa
authors.initials: ML
authors.lastname: Sagristá
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008027:Light; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008665:Metalloporphyrins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018613:Microscopy, Confocal; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D008665:Metalloporphyrins; D017319:Photosensitizing Agents; C048955:zinc tetraphenylporphyrin