m-THPC-mediated photodynamic therapy of malignant gliomas: assessment of a new transfection strategy.
Malignant gliomas represent the most common primary brain tumor: more than 50% of them are glioblastoma multiforme (GBM). Photodynamic therapy may offer a very good chance of targeted destruction of infiltrating GBM cells, thus increasing the survival time and recurrence-free interval of GBM patients. Among photosensitizing agents, meta-tetrahydroxyphenylchlorin (m-THPC) is promising for the treatment of brain tumors. In previous studies, we investigated the transfection activity of dimyristoyl-sn-glycero-phosphatidylcholine (DMPC) liposomes, containing a cationic gemini surfactant, loaded with m-THPC on human colon adenocarcinoma and glioblastoma cell lines. In this paper, the uptake and the intracellular distribution of m-THPC, loaded in several formulations of cationic liposomes, were analyzed, by making a comparison with those obtained using the same chlorin in the pharmaceutical form (Foscan(R)). Moreover, by cloning efficiency assay the potential therapeutic efficiency of chlorin delivered by liposome formulations was compared with that of the pharmaceutical compound, before and after irradiation with laser light at 652 nm. The obtained results indicated that cationic liposomes (i) transferred m-THPC in glioblastoma cells more efficiently than pharmaceutical formulation; (ii) significantly (p < 0.001) increased the m-THPC cytotoxic effect after laser irradiation; (iii) seemed to exert their cytotoxic action in the early phase of interaction with the cells, during adhesion to the plasma membrane.
Molinari
Agnese
A
Department of Technology and Health, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Bombelli
Cecilia
C
Mannino
Stefano
S
Stringaro
Annarita
A
Toccacieli
Laura
L
Calcabrini
Annarica
A
Colone
Marisa
M
Mangiola
Annunziato
A
Maira
Giulio
G
Luciani
Paola
P
Mancini
Giovanna
G
Arancia
Giuseppe
G
D001932:Brain Neoplasms / Q000188:drug therapy*; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008081:Liposomes; D008652:Mesoporphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018613:Microscopy, Confocal; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin