Immunoliposomes bearing polyethyleneglycol‐coupled Fab′ fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo

FEBS Letters

Tagawa, Toshiaki²  Iwatsuru, Motoharu¹  Takahashi, Nobuya¹  Maruyama, Kazuo¹  Nagaike, Kazuhiro² 

[1] Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-01, Japan;The Research Center, Mitsubishi Chemical Co., 1000 Kashimada-cho, Midori-ku, Yokohama 227, Japan

关键词: Liposome;    Immunoliposome;    Fab′ fragment;    Polyethyleneglycol;    Drug delivery system;    21B2;    monoclonal antibody IgG1 antibody;    specific for the human carcinoembryonic antigen;    CEA;    human carcinoembryonic antigen;    CHOL;    cholesterol;    DPPE;    dipalmitoylphosphatidylethanolamine;    DPPE-PEG;    dipalmitoyl-N-(monomethoxy polyethyleneglycol succinyl) phosphatidylethanolamine;    DPPE-PEG-COOH;    dipalmitoyl-N-(3-carboxypropionoyl polyethyleneglycol succinyl)phosphatidylethanolamine;    DPPE-PEG-Mal;    dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl group;    DSPC;    distearoylphosphatidylcholine;    MKN-45;    CEA-positive human gastric cancer cells;    RES;    reticuloendothelial system;   

DOI  :  10.1016/S0014-5793(97)00905-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have developed a new type of long-circulating immunoliposome (Fab′–PEG immunoliposomes) which is efficiently extravasated into the targeted solid tumor in vivo. Small unilamellar liposomes (100–130 nm in diameter) were prepared from distearoylphosphatidylcholine (DSPC), cholesterol (CHOL) and a dipalmitoylphosphatidylethanolamine derivative of PEG with a terminal maleimidyl group (DPPE-PEG-Mal), and conjugated Fab′ fragment of antibody. Inclusion of DPPE-PEG-Mal and linkage of the Fab′ fragment instead of intact antibody to PEG terminals allowed the liposomes to evade RES uptake and remain in the circulation for a long time, resulting in enhanced accumulation of the liposomes in the solid tumor. Because of the ability of such Fab′–PEG immunoliposomes to target solid tumors, they appear highly attractive as carriers of not only chemotherapeutic agents, but also of macromolecular drugs.

【 授权许可】

Unknown