紫草素具有诱导多种肿瘤细胞凋亡以及逆转多药耐药功能，对乳腺癌具有良好治疗作用。但紫草素为脂溶性药物且毒性较大，常规给药吸收率较低，体内分布广泛，难以集中作用于肿瘤发挥治疗作用。本课题拟合成具有温度敏感性的嵌段共聚物，并在胶束表面共价连接抗人类表皮生长因子受体2片段的抗体，形成抗体连接的双靶向纳米免疫胶束包裹紫草素。该双靶向纳米免疫胶束将具有温度响应性的被动靶向和抗体的主动靶向功能。课题将检测载紫草素的双靶向纳米免疫胶束的载药量，药物代谢和组织分布情况，观察其急慢性毒性。培养耐药乳腺癌细胞，观察其杀伤SRKB3细胞和逆转耐药能力；制备耐药荷瘤裸鼠模型，观察载紫草素的双靶向纳米免疫胶束体内抑瘤率和荷瘤裸鼠生存期，并对其作用机制进行研究。

Shikonin demonstrates excellent therapeutic effects on breast cancer because it can induce apoptosis in various tumor cells and reverse multidrug resistance. However, shikonin is a kind of lipid soluble drug with high toxicity, low absorption rate after oral administration and a widespread distribution in vitro. Thus, its anti-tumor functionality cannot be fully used. This proposal aims to synthesize temperature sensitive block copolymers, graft the anti-HER2 fab on the surface of their micelle through covalent bonding, and finally fabricate antibodies modified immune nanomicelle with double targeting functionality; shikonin will also be encapsulated in these nanomicelle. The prepared immune nanomicelle has passive targeting function due to the temperature sensitive polymer and active targeting function due to the anti-HER2 fab. With the double targeting immune nanomicelle, this proposal will test its drug loading, drug delivery efficiency, and distribution in tissues in vitro. Breast cancer cells with drug resistance will be cultured and drug resistance tumor bearing nude mice will be constructed, which can be used to study the effects of double targeting immune nanomicelle loaded with shikonin on cancer cell killing and tumor-bearing nude mice’s life cycle. The transfer process, killing effect, and anti-MDR function of shikonin in breast cancer cells with the expression of Her2 antigen will also be studied. In addation, its mechanism will also be investigated.