MODIFIED POLYVINYL ALCOHOL-BENZOPORPHYRIN DERIVATIVE CONJUGATES AS PHOTOTOXIC AGENTS

被引:16
作者
DAVIS, N
LIU, D
JAIN, AK
JIANG, SY
JIANG, F
RICHTER, A
LEVY, JG
机构
[1] UNIV BRITISH COLUMBIA,DEPT MICROBIOL,300-6174 UNIV BLVD,VANCOUVER V6T 1Z3,BC,CANADA
[2] QUADRA LOG TECHNOL INC,VANCOUVER V5Z 4H5,BC,CANADA
[3] SHANGHAI MED UNIV,DEPT CHEM,SHANGHAI,PEOPLES R CHINA
关键词
D O I
10.1111/j.1751-1097.1993.tb02930.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Photosensitizing and biodistribution characteristics of a photosensitizer (benzoporphyrin derivative, monoacid ring A; BPD) conjugated to a macromolecule (modified polyvinyl alcohol; M-PVA, molecular weight = 10 000) 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) tumors was tested in an in vivo/in vitro assay, in which tumor-bearing mice were injected intravenously with free or conjugated H-3-BPD and 3 h later light activation of tumor cells was carried out in vitro. Biodistribution studies were carried out using MI tumor-bearing DBA/2 mice and 3H-BPD either free or conjugated to M-PVA. The results of these studies showed that the conjugation of BPD to M-PVA resulted in the formation of a macromolecular photosensitizer that retained full photosensitizing activity of the photosensitizer molecules and at the same time gained new characteristics, advantageous for 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 comparable to free BPD, the conjugate (1:25) reached slightly higher levels 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 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.
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收藏
页码:641 / 647
页数:7
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