A two-step pretargeting approach composed of biotinylated antibody and streptavidin modified liposomes to target tumor necrotic regions
Tumor Necrosis Treatment (TNT) was developed to target solid tumors using monoclonal antibodies such as chimeric TNT-3 monoclonal antibody (chTNT-3), which bind to degenerating cells located in necrotic regions of tumors. Since biotinylated chTNT-3 showed shorter circulating time and more uptakes in tumors than unmodified chTNT-3, we designed the two-step pretargeting approach composed of administering biotinylated chTNT-3 and 24h later administering streptavidin modified liposomes encapsulating doxorubicin (DOX) to deliver DOX to the tumor site. The preservation of immunoreactivity of biotinylated chTNT-3 was confirmed by ELISA. The biological half-life of total DOX in two-step pretargeting approach was longer than that of flee DOX but shorter than that of sterically stabilized liposomes in Sprague-Dawley rats. The two-step pretargeting approach regimen showed a good targeting effect to tumors with a gradual process in biodistribution study. At 4h and 24h after administering DOX-loaded liposomes a highest DOX level of the two-step pretargeting approach was observed. And it showed the best antitumor efficacy 3 days after the second treatment in Balb/c nude mice bearing H460 tumors. These results suggested the two-step pretargeting approach regimen may be a new form that could be used for delivering anticancer drugs to tumor necrotic regions.
Tumor necrosis treatment biotinylated antibody pretargeting streptavidin sterically stabilized liposomes
Hong Pan Limei Hana Wei Chen Ming Yao Weiyue Lu
Department of Pharmaceutics, School of Pharmacy, Fudan University, 200032 Shanghai, China;Central Re Department of Pharmaceutics, School of Pharmacy, Fudan University, 200032 Shanghai, China Department of Experimental Pathology, Institute of Oncology, Shanghai Jiao Tong University, 200032 S
国际会议
上海
英文
130-139
2007-10-19（万方平台首次上网日期，不代表论文的发表时间）