MODIFIED POLYVINYL ALCOHOL-BENZOPORPHYRIN DERIVATIVE CONJUGATES AS PHOTOTOXIC AGENTS

Photosensitizing and biodistribution characteristics of a photosensiti zer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 1 0 000) were tested in vitro and in vivo. Modified PVA was loaded with BPD at molar ratios 1:12, 1:25, 1:50, 1:75 and 1:100. Most of the work was carried out with a conjugate having a 1:25 molar ratio. In vitro photosensitization was tested using A549 (human lung carcinoma), A432 (human epidermoid carcinoma) and P815 (mastocytoma of DBA/2 mice) cell lines. Photosensitization of MI (rhabdomyosarcoma of DBA/2 mice) tumo rs was tested in an in vivo/in vitro assay, in which tumor-bearing mic e were injected intravenously with free or conjugated H-3-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodis tribution studies were carried out using MI tumor-bearing DBA/2 mice a nd 3H-BPD either free or conjugated to M-PVA. The results of these stu dies showed that the conjugation of BPD to M-PVA resulted in the forma tion of a macromolecular photosensitizer that retained full photosensi tizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for photodynamic treatment, e specially in vivo. In vitro M-PVA-BPD conjugates were at least as effi cient in photosensitization of tumor cells as an equivalent number of free BPD molecules, both in the presence and in the absence of serum. Although the biodistribution was in general comparable to free BPD, th e conjugate (1:25) reached slightly higher levels in the blood, kidney , lung and spleen, and lower levels in the liver, brain, skin and musc le in comparison with free BPD. Although the level of M-PVA-BPD in tum or tissue was lower than that of free BPD under comparable conditions, the conjugate was bound more tightly to the tumor cells and effected higher tumor cell kill when activated by light.