TARGETING LIPOSOMES FOR SELECTIVE INTERACTION WITH SPECIFIC CELLS AND TISSUES

我们研究了三种概念上不同的“瞄准”方式 脂质体： (1)抗体介导的靶向。 我们发现携带抗体的 脂质体大量地结合到携带脂质体的细胞上。 合适的抗原。 然而，结合的脂质体是 只有当内吞作用是可能的时候才内化。 内吞作用后， 脂质体包埋的甲氨蝶呤（MTX）可以从 内吞器并结合细胞质二氢叶酸 还原酶，抑制细胞生长。 在这些过程中， 研究中，我们开发了第一个异双功能方法， 将抗体偶联至脂质体。 目前的研究是针对 艾滋病病毒感染的细胞。 (2)物理瞄准。 我们设计了“温度敏感” 脂质体，其分解并选择性地释放截留的 药物在体内的温度可达到局部热疗。 这些脂质体在体内选择性地将MTX递送至小鼠肿瘤 抑制它们的生长 (3)分区瞄准。 我们已经展示了 脂质体和包埋的药物递送到淋巴结 皮下和腹膜内，注射，并已确定 细胞定位点 这些研究已经扩展到 携带抗体的脂质体。

We have studied three conceptually different ways of "targeting" liposomes: (1) Antibody-mediated targeting. We find that antibody-bearing liposomes bind in large numbers to cells which bear the appropriate antigen. However, the bound liposomes are internalized only if endocytosis is possible. Upon endocytosis, liposome-entrapped methotrexate (MTX) can escape from the endocytic apparatus and bind to cytoplasmic dihydrofolate reductase, inhibiting growth of the cell. In the course of these studies, we developed the first heterobifunctional method for coupling antibody to liposomes. Current studies are directed toward HIV-infected cells. (2) Physical targeting. We have designed "temperature-sensitive" liposomes, which break down and selectively release an entrapped drug in vivo at temperatures achievable by local hyperthermia. These liposomes selectively deliver MTX to mouse tumors in vivo and inhibit their growth. (3) Compartmental targeting. We have demonstrated the delivery of liposomes and entrapped drug to lymph nodes after subcutaneous and intraperitoneal, injection and have determined cellular sites of localization. These studies have been extended to antibody-bearing liposomes.