Experimental photodynamic therapy with MESO-tetrakisphenylporphyrin (TPP) in liposomes leads to disintegration of human amelanotic melanoma implanted to nude mice.
Liposomal meso-tetrakis-phenylporphyrin (TPP) was tested for photodynamic therapy (PDT) of human amelanotic melanomas implanted in nude mice. After intratumoural TPP application (15 mg x kg(-1)) followed by PDT lamp irradiation (600-700 nm, 635 nm peak), tumours retained their original volume up to the 23rd day post-PDT, whereas volumes increased 6 times in controls. PDT with intravenously (i.v.) administered liposomal (3.2 mg x kg(-1)) TPP mostly disintegrated tumours to zero volumes. Melanoma remissions were accompanied by tumour surface necroses and were documented by the appearance of nontumourous cells with nonpycnotic nuclei. Spatial arrangement of capillaries in remissing tumour was the same as in healthy surrounding tissue. Lower TPP doses (1, 0.3 and 0.1 mg x kg(-1)) were more or equally efficient than hydrophilic TPPS(4) (3.2 mg x kg(-1), i.e., sulfonated TPP), i.v. administered also in liposomes. Liposomal TPPS(4) only delayed the onset of subsequent tumour growth. Commercial Photosan 3 disintegrated tumours only in doses of approx. 7.5 mg x kg(-1); in lower doses it was less efficient than TPPS(4). The second PDT cycle (3.2 mg x kg(-1) TPP or 7.5 mg x kg(-1) Photosan 3), performed in a few unsuccessfully cured mice, predominantly led again to tumour remissions. Since the measured TPP and TPPS(4) content in melanomas was similar, these results demonstrate the advantage of PDT with a hydrophobic photosensitizer such as TPP. Photophysical properties of TPP and TPPS(4) are equal, but TPP has probably more favorable intracellular distribution, as documented by our studies, which leads to more efficient PDT. Consequently, liposomal TPP is suggested as a potentially suitable efficient preparation for PDT.
Jezek
Petr
P
Department of Membrane Transport Biophysics, Institute of Physiology, Academy of Sciences, Prague, Czech Republic. jezek@biomed.cas.cz
Nekvasil
Milos
M
Skobisová
Eva
E
Urbánková
Eva
E
Jirsa
Milan
M
Zadinová
Marie
M
Poucková
Pavla
P
Klepácek
Ivo
I
D000818:Animals; D004337:Drug Carriers; D005260:Female; D006801:Humans; D015552:Injections, Intralesional; D007275:Injections, Intravenous; D008081:Liposomes; D018328:Melanoma, Amelanotic / Q000188:drug therapy* / Q000473:pathology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D011166:Porphyrins / Q000627:therapeutic use*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
D004337:Drug Carriers; D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; C092400:meso-tetrakis(4-sulfonatophenyl)porphyrin