MODIFIED POLYVINYL ALCOHOL-BENZOPORPHYRIN DERIVATIVE CONJUGATES AS PHOTOTOXIC AGENTS

Abstract— Photosensitizing and biodistribution characteristics of a photosensitizer(benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight=10000) 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 M1 (rhabdomyosarcoma of DBA/2 mice) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated ³H-BPD and 3 h later light activation of tumor cells was carrie out in vitro . Biodistribution studies were carried out using M1 tumor-bearing DBA/2 mice and ³H-BPD either free or conjugated to M-PVA. The result of there these studies showed that the conjugatin of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing avtivity of the photosensitizer molecules and at the same time gained new charcteristics, advantageous from photodynamic treatment, especially in vivo . In vitro M-PVA-BPD conjugates were at least as efficient 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 comparabel to free BPD, the conjugate(1:25) reached slightly higher leves in the blood, kidney, lung and spleen, and lower levels in the liver, brain, skin and muscle in comparison with free BPD. Although the level of M-PVA-BPD in tumor tissue was lower than tht 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