title: Photodynamic effects of zinc(II) phthalocyanine-loaded polymeric micelles in human nasopharynx KB carcinoma cells.
abstract: A major difficulty in photodynamic therapy is the poor solubility of the photosensitizer (PS) under physiological conditions which correlates with low bioavailability. PS aggregation leads to a decrease in the photodynamic efficiency and a more limited activity in vitro and in vivo. To improve the aqueous solubility and reduce the aggregation of 2,9(10),16(17),23(24)-tetrakis[(2-dimethylamino)ethylsulfanyl]phthal-ocyaninatozinc(II) (Pc9), the encapsulation into four poloxamine polymeric micelles (T304, T904, T1107 and T1307) displaying a broad spectrum of molecular weight and hydrophilic-lipophilic balance was investigated. The aqueous solubility of Pc9 was increased up to 30 times. Morphological evaluation showed the formation of Pc9-loaded spherical micelles in the nanosize range. UV/Vis and fluorescence studies indicated that Pc9 is less aggregated upon encapsulation in comparison with Pc9 in water-DMSO 2% and remained photostable. Pc9-loaded micelles generated singlet molecular oxygen in high yields. Photocytotoxicity assays using human nasopharynx KB carcinoma cells confirmed that the encapsulation of Pc9 in T1107 and T1307 increases its photocytotoxicity by 10 times in comparison with the free form in water-DMSO. In addition, Pc9 incorporated into cells was mainly localized in lysosomes.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: García Vior
authors.forename: Julieta
authors.initials: J
authors.lastname: Marino
authors.forename: Leonor P
authors.initials: LP
authors.lastname: Roguin
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
authors.forename: Josefina
authors.initials: J
authors.lastname: Awruch
mesh_terms: D001692:Biological Transport; D002277:Carcinoma; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D004339:Drug Compounding; D005029:Ethylenediamines / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology*; D054833:Isoindoles; D007624:KB Cells; D008027:Light; D008823:Micelles; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000473:pathology; D009305:Nasopharynx / Q000187:drug effects / Q000473:pathology; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D026082:Singlet Oxygen; D012995:Solubility; D014867:Water; D017967:Zinc Compounds
chemical_list: D003603:Cytotoxins; D005029:Ethylenediamines; D007211:Indoles; D054833:Isoindoles; D008823:Micelles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011108:Polymers; D017967:Zinc Compounds; D014867:Water; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen