目的:构建对紫外线反应的靶向人类表皮生长因子2(human epidermal growth factor receptor 2,HER-2)的免疫脂质体,提高化疗药物对乳腺癌细胞的杀伤效果。方法:薄膜分散法制备脂质体,表面修饰上抗HER-2抗体(曲妥珠单抗)的Fab片段,并将脂质体用紫外线进行交联,制备光敏免疫脂质体。透射电镜观察脂质体的形态,动态光散射测定脂质体的粒径和血液学稳定性,倒置荧光显微镜和流式细胞术检测乳腺癌细胞MCF-7对脂质体药物的摄取能力,CCK-8试剂盒测定并比较脂质体与游离药物对乳腺癌细胞的体外杀伤效应,皮下肿瘤抑制实验比较脂质体药物与游离药物对乳腺癌细胞的体内杀伤效应。结果:本研究制备出的对紫外线敏感的HER-2靶向脂质体具有规整的球状结构、合适的粒径大小和较强的稳定性。乳腺癌细胞MCF-7对免疫脂质体的摄取能力较非靶向脂质体和游离DOX显著增强(P均<0.05)。进一步研究显示,光敏免疫脂质体药物对MCF-7细胞的体外杀伤能力明显优于非靶向脂质体药物和游离药物(P均<0.05)。体内研究结果显示,与非靶向脂质体药物和游离药物相比,免疫脂质体药物能够显著降低荷瘤小鼠的皮下肿瘤负荷(P均<0.05)。结论:本研究制备的靶向HER-2的光敏免疫脂质体拥有较好的稳定性和极强的肿瘤杀伤效果,具有广阔的临床应用前景。 OBJECTIVE: To construct an immunoliposome that targets human epidermal growth factor receptor 2 (HER-2) in response to ultraviolet light and enhance the killing effect of chemotherapeutic drugs on breast cancer cells. Methods: The liposomes were prepared by the membrane dispersion method. The Fab fragments of anti-HER-2 antibody (trastuzumab) were surface-modified and the liposomes were cross-linked by UV light to prepare photosensitive immunoliposomes. The morphology of liposomes was observed by transmission electron microscopy, the particle size and hematological stability of liposomes were determined by dynamic light scattering, the uptake of liposomal drug by MCF-7 was detected by inverted fluorescence microscope and flow cytometry, CCK -8 kit for the determination and comparison of liposomes and free drugs on human breast cancer cells in vitro killing effect, subcutaneous tumor inhibition experiments compared liposomal drugs and free drugs on breast cancer cells in vivo killing effect. Results: The UV-sensitive HER-2 targeted liposomes prepared in this study have regular spherical structure, suitable particle size and strong stability. Breast cancer cells MCF-7 uptake of immune liposomes than non-targeted liposomes and free DOX was significantly enhanced (P all <0.05). Further studies showed that the photosensitized immunoliposomal drug against MCF-7 cells in vitro cytotoxicity was significantly superior to non-targeted liposomal drug and free drug (P all <0.05). In vivo studies showed that, compared with non-targeted liposomal drug and free drug, immunoliposomal drug can significantly reduce the subcutaneous tumor burden in tumor-bearing mice (all P <0.05). Conclusion: The immunosensor targeting HER-2 prepared in this study has good stability and strong tumor killing effect, and has broad clinical application prospects.