Kullberg Max, Mann Kristine, Owens Jesse Lee
Biomedical Program, University of Alaska, Anchorage, AK 99508, USA.
J Drug Target. 2009 Feb;17(2):98-107. doi: 10.1080/10611860802471562.
We report on a new method for enhancing the specificity of drug delivery for tumor cells, using thermosensitive immunoliposomes. The liposomes are conjugated to the antibody trastuzumab (Herceptin), which targets the human epidermal growth factor receptor 2 (Her-2), a cell membrane receptor overexpressed in many human cancers. Being thermosensitive, the liposomes only release their contents when heated slightly above body temperature, allowing for the possibility of tissue targeting through localized hyperthermia. Using self-quenching calcein, we demonstrate the release of liposome contents into cell endosomes after brief heating to 42 degrees C. To further increase targeting specificity, we incorporate the concept of a two-component delivery system that requires the interaction of two different liposomes within the same endosome for cytoplasmic delivery. Experimental evaluation of the technique using fluorescently labeled liposomes shows that a two-component delivery system, combined with intracellular disruption of liposomes by hyperthermia, significantly increases specificity for Her-2-overexpressing tumor cells.
我们报道了一种使用热敏免疫脂质体提高肿瘤细胞药物递送特异性的新方法。脂质体与靶向人表皮生长因子受体2（Her-2）的抗体曲妥珠单抗（赫赛汀）偶联，Her-2是一种在许多人类癌症中过度表达的细胞膜受体。由于具有热敏性，脂质体仅在体温略高于正常体温时释放其内容物，这使得通过局部热疗实现组织靶向成为可能。使用自猝灭的钙黄绿素，我们证明了在短暂加热至42摄氏度后，脂质体内容物释放到细胞内体中。为了进一步提高靶向特异性，我们引入了双组分递送系统的概念，该系统需要同一内体中的两种不同脂质体相互作用才能进行细胞质递送。使用荧光标记脂质体对该技术进行的实验评估表明，双组分递送系统与热疗引起的脂质体细胞内破坏相结合，可显著提高对Her-2过表达肿瘤细胞的特异性。
