Novel topical photodynamic therapy of prostate carcinoma using hydroxy-aluminum phthalocyanine entrapped in liposomes.

BACKGROUND: Clinically-approved anticancer photodynamic therapy (PDT) is now extensively studied for various cancer diagnoses. We focused on the treatment efficacy of topical administration of hydroxy-aluminum phthalocyanine (AlOH-PC) entrapped in liposomes against in vivo models of prostate carcinomas. MATERIALS AND METHODS: LNCaP and PC3 cells were subcutaneously injected into the right flank of athymic nude mice. Mice with grown tumours were used for in vivo efficacy studies. Firstly, we applied different doses of AlOH-PC to less aggressive LNCaP tumours to determine the effective dose. In later studies, we focused on more aggressive prostate tumours (PC3) using doses of liposomal-AlOH-PC gel formulation. Topical application of photosensitizers was followed by PDT irradiation (600-700 nm, 635 nm peak). Tumour growth was measured three times-a-week. RESULTS: Comparison of PDT of aggressive PC3 and less aggressive LNCaP prostate carcinomas showed that both tumour types are sensitive and treatable by liposomal formulation of AlOH-PC. For LNCaP tumours the efficient dose (100% experimental animals cured, n=8/8) was 4.5 mg/ml of AlOH-PC in the gel. Whereas, in the case of PC3 carcinomas, a dose of 4 mg/ml significantly postponed tumour growth, but no animals were cured (n=0/8); a sufficient curative dose (100% mice cured, n=8/8) was 6 mg/ml of AlOH-PC in the gel. CONCLUSION: Liposomal AlOH-PC gel has potential for effective PDT of prostate carcinomas.

Evaluation of topical photodynamic therapy of mammary carcinoma with an experimental gel containing liposomal hydroxyl-aluminium phthalocyanine.

BACKGROUND: Photodynamic therapy (PDT) is a clinically-accepted approach for the therapy of many types of cancer. This study focused on the treatment of mammarian carcinoma by topical administration of hydroxyl-aluminium phthalocyanine (AlOH-PC), compared to a clinically-approved photosensitizer (Metvix, Galderma & PhotoCure ASA, Inc., Oslo, Norway). MATERIALS AND METHODS: MDA-MB 231 cells were subcutaneously injected into the right flank of athymic nude mice. Mice with grown tumours were used for in vivo efficacy studies. Different doses of liposomal AlOH-PC were applied to determine the most effective dose. In later studies, Metvix or our liposomal-AlOH-PC gel formula were used. Topical application of photosensitizers was followed by the PDT irradiation at 600-700 nm (635 nm peak). Tumour growth was measured three times weekly. RESULTS: Therapeutic studies revealed that AlOH-PC treatment led to complete tumour remission in 90% (9/10) of experimental animals, whereas usage of the commercially available Metvix only postponed the tumour growth. Moreover, usage of liposomal AlOH-PC shortened the time allowed between the application of the photosensitizer and light exposure: for Metvix, hours are usually needed, while the tested liposomal AlOH-PC showed remarkable outcomes after only 10 min. CONCLUSION: Liposomal AlOH-PC gel appears to be potentially suitable for PDT of mammarian carcinoma.

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.