A series of liposome ligands (Bio-Chol, Bio-Bio-Chol, tri-Bio-Chol and tetra-Bio-Chol) modified by different branched biotins that can recognize the SMVT receptors over-expressed in breast cancer cells were synthesized. And four liposomes (Bio-Lip, Bio-Bio-Lip, tri-Bio-Lip and tetra-Bio-Lip) modified by above mentioned ligands as well as the unmodified liposome (Lip) were prepared to study the targeting ability for breast cancer. The cytotoxicity study and apoptosis assay of paclitaxel-loaded liposomes showed that tri-Bio-Lip had the strongest anti-proliferative effect on breast cancer cells. The cellular uptake studies on mice breast cancer cells (4T1) and human breast cancer cells (MCF-7) indicated tri-Bio-Lip possessed the strongest internalization ability, which was 5.21 times of Lip, 2.60 times of Bio-Lip, 1.67 times of Bio-Bio-Lip and 1.17 times of tetra-Bio-Lip, respectively. Moreover, the 4T1 tumor-bearing BALB/c mice were used to evaluate the in vivo targeting ability. The data showed the enrichment of liposomes at tumor sites were tri-Bio-Lip > tetra-Bio-Lip > Bio-Bio-Lip > Bio-Lip > Lip, which were consistent with the results of in vitro targeting studies. In conclusion, increasing the density of targeting molecules on the surface of liposomes can effectively enhance the breast cancer targeting ability, and the branching structure and spatial distance of biotin residues may also have an important influence on the affinity to SMVT receptors. Therefore, tri-Bio-Lip could be a promising drug delivery system for targeting breast cancer.

合成了一系列脂质体配体（Bio-Chol，Bio-Bio-Chol，tri-Bio-Chol和tetra-Bio-Chol），这些配体经不同的分支生物素修饰，可以识别乳腺癌细胞中过度表达的SMVT受体。并制备了经上述配体修饰的四个脂质体（Bio-Lip，Bio-Bio-Lip，tri-Bio-Lip和tetra-Bio-Lip）以及未修饰的脂质体（Lip），以研究对乳腺癌的靶向能力。紫杉醇脂质体的细胞毒性研究和细胞凋亡检测表明tri-Bio-Lip对乳腺癌细胞具有最强的抗增殖作用。对小鼠乳腺癌细胞（4T1）和人乳腺癌细胞（MCF-7）的细胞摄取研究表明，tri-Bio-Lip具有最强的内在化能力，分别是Lip的5.21倍，Bio-Lip的2.60倍，1.67倍Bio-Bio-Lip和1。四倍Bio-Lip的17倍。此外，使用4T1荷瘤BALB / c小鼠评估了体内靶向能力。数据显示脂质体在肿瘤部位的富集为三-生物脂质>四-生物脂质>生物-生物脂质>生物-脂质>嘴唇，这与体外靶向研究的结果一致。总之，增加脂质体表面靶向分子的密度可以有效增强乳腺癌的靶向能力，生物素残基的分支结构和空间距离也可能对SMVT受体的亲和力产生重要影响。因此，tri-Bio-Lip可能是针对乳腺癌的有前途的药物输送系统。