新胡萝卜素
高分子
化学
白蛋白
血管通透性
体外
血液蛋白质类
血清白蛋白
淋巴系统
生物化学
生物物理学
分子生物学
DNA
生物
病理
免疫学
医学
作者
Yasuhiro Matsumura,Tatsuya Oda,Hironori Maeda
出处
期刊:PubMed
日期:1987-03-01
卷期号:14 (3 Pt 2): 821-9
被引量:38
摘要
Selective tumor targeting of anticancer agents is critically important in cancer chemotherapy. We previously found that a polymer-conjugated anticancer protein (neocarzinostatin; NCS), named smancs, accumulated more in tumor tissues than did NCS. In order to determine the general mechanism of this tumoritropic accumulation of smancs and other proteins, we used radioactive (51Cr-labeled) proteins with various molecular sizes (12-160 kDa) and other properties. In addition, we used dye-complexed serum albumin to visualize its accumulation in tumors of tumor-bearing mice. Many proteins progressively accumulated in the tumor tissues of the mice, and a ratio of the protein concentration in the tumor to that in the blood (T/B) of 5 was readily obtained within 6-48 h. A large protein like IgG required a longer time (72 h) to reach this value of 5. A T/B value of neither 1 nor 5 was achieved at a significant concentration with NCS, a representative small protein (12 kDa), at any time. We speculate that the tumoritropic accumulation of these proteins occurred because of hypervasculature and enhanced vascular permeability to even macromolecules, with little recovery through either blood vessels or lymphatic vessels from the tumor tissue. This accumulation of macromolecules in the tumor was also found after intravenous injection of dye (Evans blue) which was bound mostly to albumin. Thus, the albumin-dye complex was retained only in the tumor tissue for prolonged periods. There was little lymphatic recovery of macromolecules from tumor tissue. When this complex prepared in vitro was injected into the tumor and normal tissue, the latter tissue cleared it completely within 48 h whereas the tumor tissue retained most of it. The difference between the clearance from the tumor and that from normal tissue was based on the difference in lymphatic drainage of the two tissues. The present finding is of potential value in macromolecular tumor therapeutics and diagnosis. We propose this general mechanism of the behavior of macromolecules and lipids as EPR (enhanced permeability and retention) effect in solid tumor at microvasculature level.
科研通智能强力驱动
Strongly Powered by AbleSci AI