On the mechanism of the tumour-localising effect in photodynamic therapy.

The proposed mechanisms by which tumours concentrate photosensitisers are reviewed. Tumour-associated macrophages have been shown by others to accumulate up to nine times the level of porphyrins as do tumour cells. Macrophages also take up and degrade oxidised or otherwise modified low-density lipoprotein (LDL). We propose that the interaction of photosensitisers with LDL is an important factor, leading to accumulation in macrophages. Uptake into these cells via liposomes and high-density lipoprotein is also possible. There may be three separate mechanisms for tumour destruction in photodynamic therapy: (i) direct damage to tumour cells; (ii) damage to the endothelial cells of the tumour microvasculature; and (iii) macrophage-mediated immune infiltration of the tumour. The association of photosensitisers with lipoproteins may accentuate the latter two (endothelial cells can also accumulate modified lipoproteins). Accumulation in macrophages may also largely explain the high porphyrin retention observed in atheromatous plaques.