An Ultrastructural Comparative Evaluation of Tumors Photosensitized by Porphyrins Administered in Aqueous Solution, Bound to Liposomes or to Lipoproteins

Balb/c mice bearing a transplantedMS–2 fibrosarcoma have been injected with 2 mg kg‐1 hematoporphyrin either dissolved in phosphate‐buffered saline (Hp‐aq), or incorporated into unilamellar liposomes of dipalmitoyl‐phosphatidylcholine (Hp‐lip), or precomplexed with low density lipoproteins (Hp‐LDL). At 24 h after injection, the mice received 150 J cm‐2 of600–680 nm light irradiation. Electron microscopic studies performed on tumor tissues taken from mice sacrificed at different times after the phototreatment showed that, in the presence of Hp‐aq. tumor necrosis is largely the consequence of vascular damage. On the other hand, in the presence of Hp‐lip and Hp‐LDL, the response of the tumor to the phototreatment occurs at a faster rate and is mainly determined by direct damage of neoplastic cells. These findings are correlated with the different distribution of the various hematoporphyrin forms (Hp‐aq, Hp‐lip, Hp‐LDL) among the serum proteins and the modalities of hematoporphyrin delivery to tissues by the possible carriers.