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.