Photothermal sensitisation and therapeutic properties of a novel far-red absorbing cyanine.
A water-soluble disulfonate cyanine was prepared by chemical synthesis and shown to possess photophysical properties which are particularly favourable for the promotion of photothermally sensitised processes, including a very low (<0.1) quantum yield of fluorescence emission and ultra-short (110 to 400 ps) excited state lifetimes, as well as the presence of intense absorption bands at wavelengths longer than 800 nm. This allows the possibility of high-energy irradiation by means of a Ti:sapphire laser operated in a pulse regime. The cyanine was accumulated in comparable amounts by B78H1 amelanotic melanoma cells and HT1080 transformed fibroblasts, however only the B78H1 cells could be extensively damaged by photothermal sensitisation with the cyanine, which was endocellularly distributed as suggested by observations at the optical microscope; the efficiency of the photoprocess could be enhanced by formation of aggregated intracellular cyanine clusters. On the other hand, only a modest photoinactivation of HT1080 cells was induced by photothermal sensitisation, possibly owing to the localization of the cyanine at the periphery of such cells. The cyanine also exhibited a good selectivity of amelanotic melanoma targeting in C57BL/6 mice, bearing the tumour subcutaneously transplanted in the dorsal area: the ratio of cyanine concentration in the melanoma and the surrounding cutaneous districts was as large as 3.8 at 1 h post-injection. The cyanine underwent a fast clearance from the organism, since only traces of the photosensitiser were observed in all the studied tissues at 3 h after i.v. administration. Thus, irradiations were performed at post-injection times shorter than 1 h. Maximum photothermal sensitisation efficiency was obtained at 10 min after injection with a 50% cure rate. Thus, photothermal therapy (PTT) appears to be a very promising and efficient modality of tumour treatment.
Department of Biology, University of Padova, Padova, Italy. monica.camerin@unipd.it
Monica
M
Camerin
Giulio
G
Jori
Leopoldo
L
Della Ciana
Serena
S
Fabbroni
Sara
S
Bonacchi
Marco
M
Montalti
Luca
L
Prodi
D000042:Absorption; D000818:Animals; D002232:Carbocyanines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003116:Color; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008027:Light; D018328:Melanoma, Amelanotic / Q000473:pathology / Q000628:therapy; D051379:Mice; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D010789:Phototherapy
D002232:Carbocyanines; C547092:FS308; D017319:Photosensitizing Agents