THE EFFECTS OF PLASMA LIPOPROTEINS ON in vitro TUMOR CELL KILLING and in vivo TUMOR PHOTOSENSITIZATION WITH BENZOPORPHYRIN DERIVATIVE

Abstract

The influence of lipoprotein association on in vitro tumor cell killing and in vivo tumor photosensitization with benzoporphyrin derivative (BPD) has been investigated in M-1 tumor bearing mice. The association of benzoporphyrin mono acid ring A with either low or high density lipoprotein increased tumor cell killing in an in vivo/in vitro cytotoxicity assay performed 3 h post intravenous drug administration. Eight hours following photosensitizer injection only low density lipoprotein (LDL) mixtures produced significant (P less than or equal to 0.005) increases in tumor cell killing compared to BPD in unfractionated plasma. The efficacy of in vivo photosensitization in the presence of lipoproteins correlated with the in vivo/in vitro cytotoxicity. Association of BPD with low or high density lipoproteins resulted in delayed tumor regrowth and higher cure rates when light exposure (125J/cm2) was performed 3 h post drug administration. When light exposure was performed 8 h post-injection only LDL-BPD mixtures led to enhanced tumor eradication compared to BPD administered in aqueous solution or unfractionated plasma.

Evidence for low-density lipoprotein receptor-mediated uptake of benzoporphyrin derivative

“…Results of in vivo studies on the distribution, elimination and cytotoxic effects of photosensitisers in experimental tumours have been explained by eluding to the mechanism of LDL receptor-mediated endocytosis of photosensitisers, without experimental confirmation of the process (Kessel, 1986;Maziere et al, 1990;Allison et al, 1991;Richter et al, 1991). Our in vivo studies have extended the observations of LDL receptormediated accumulation of BPD in vitro to a credible mechanism for the delivery of BPD to tumour tissue in vivo.…”

High efficiency of benzoporphyrin derivative in the photodynamic therapy of pigmented malignant melanoma

“…5.5 µmol of BPD-MA kg -1 body weight. This dosage was chosen because previous reports (Allison et al, 1991) have shown that this amount of BPD-MA is effective in the PDT of other experimental tumours. Moreover, our initial investigations on the PDT of melanotic melanoma with SiNc (Biolo et al, 1996) were successfully carried out by administration of 0.64 µmol kg -1 photosensitizer; as the extinction coefficient of SiNc and BPD-MA at the wavelengths used for their in vivo excitation are 557 000 M -1 cm -1 (773 nm) and 33 000 M -1 cm -1 (690 nm), respectively, the injection of an approximately 8.5-fold larger dose of BPD-MA should compensate, at least in principle, for the lower efficiency of light absorption.…”

Photodynamic parameters in the chick chorioallantoic membrane (CAM) bioassay for topically applied photosensitizers

“…The present study is limited to four compounds: sulfonated chloro-aluminum phthalocyanine (AlPcS n ) [14], benzoporphyrin derivative monoacid ring A (BPD-MA) [15,16], lutetium texaphyrin (Lutex) [17][18][19], and aminolevulinic acid (ALA), a precursor of the endogenous sensitizer protoporphyrin IX (PpIX) [20]. In Table 1 Thursday we present some published results of the PDT efficiency, relative to Photofrin, of these selected sensitizers [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38].…”