Interaction of Free and Liposome-Bound Porphyrins with Normal and Malignant Cells: Biochemical and Photosensitization Studies in Vitro and in Vivo
The porphyrins used in combination with visible light for the early diagnosis and phototherapy of neoplasias are so far limited to hematoporphyrin (Hp) alone or associated with some derivatives obtained by acid treatment (HpD). Several evidences indicate that the cytoplasmic membrane represents a hydrophobic barrier limiting the uptake of HpD and, to a greater extent, of Hp by cells; in most cases, a significant aliquot of cell-bound porphyrin is rapidly cleared from both isolated cells1 and animal tissue2. The release is markedly slower for malignant cells and tissues3 thus providing favourable tumor-to-normal tissue ratios of porphyrin concentrations, which are exploited in diagnostic and therapeutic oncology. Clearly, further enhancements of these ratios would be of paramount clinical importance. In this paper, we report some experimental indications that liposome-bound hematoporphyrin (Hplip) and its water-insoluble dimethylester (HpDME) are taken up by cells and tissues at a higher rate and in greater amounts as compared with aqueous Hp solutions (Hpaq) of corresponding concentrations. Moreover, the release from the cells of porphyrins vehiculated via liposomes is slower.
KeywordsNeoplastic Cell Normal Hepatocyte Hydrophobic Barrier Liver Origin Porphyrin Concentration
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