[General mechanism of intratumor accumulation of macromolecules: advantage of macromolecular therapeutics].

摘要: Selective tumor targeting of anticancer agents is critically important in cancer chemotherapy. We previously found that a polymer-conjugated protein (neocarzinostatin; NCS), named smancs, accumulated more tissues than did NCS. In order to determine the general mechanism this tumoritropic accumulation smancs and other proteins, we used radioactive (51Cr-labeled) proteins with various molecular sizes (12-160 kDa) properties. addition, dye-complexed serum albumin visualize its tumors tumor-bearing mice. Many progressively mice, ratio concentration blood (T/B) 5 was readily obtained within 6-48 h. A large like IgG required longer time (72 h) reach value 5. T/B neither 1 nor achieved at significant NCS, representative small (12 kDa), any time. speculate these occurred because hypervasculature enhanced vascular permeability even macromolecules, little recovery through either vessels or lymphatic from tissue. This macromolecules also after intravenous injection dye (Evans blue) which bound mostly albumin. Thus, albumin-dye complex retained only tissue for prolonged periods. There When prepared vitro injected into normal tissue, latter cleared it completely 48 h whereas most it. The difference between clearance based on drainage two tissues. present finding potential macromolecular therapeutics diagnosis. propose behavior lipids as EPR (enhanced retention) effect solid microvasculature level.