目的 根据三阴性乳腺癌（triple negative breast cancer，TNBC）细胞过度表达葡萄糖转运蛋白1（glucose transporter type 1，Glut1），而人参皂苷Rg₃（ginsenoside Rg₃，Rg₃）的葡萄糖基可与Glut1底物高度结合的特点，以Rg₃为脂质体膜材，制备包载雷公藤红素（celastrol，Cel）的靶向治疗TNBC的脂质体（Cel/Rg₃-LPs），并对其靶向行为及抗TNBC疗效进行考察。方法 采用薄膜分散法制备Cel/Rg₃-LPs并采用单因素考察法优化处方，对优化处方的Cel/Rg₃-LPs进行形态、粒径、ζ电位、体外释放和稳定性的考察；通过Cel/Rg₃-LPs在体外鼠源4T1细胞的摄取实验、及对BALB/c原位荷4T1瘤株小鼠的治疗效果综合评价其靶向性。结果Cel/Rg₃-LPs优化处方为水化温度50 ℃，Cel为1.5 mg，Rg₃为3.0 mg，大豆磷脂为21.0 mg，制备得到的脂质体外观呈圆球形，分布均匀，其粒径和PDI分别为（148.4±0.23）nm和0.19±0.01，ζ电位为（−29.70±0.34）mV，Cel在脂质体中包封率为（96.69±0.03）%，载药量为（5.62±0.01）%。Cel/Rg₃-LPs在4T1细胞中的摄取作用显著增强，且显著抑制4T1细胞增殖；原位荷瘤小鼠体内实验表明，Cel/Rg₃-LPs能降低肿瘤组织脂质，并明显抑制肿瘤生长，具有良好的肿瘤靶向性，无明显肝肾毒性和组织毒性。结论 利用Rg₃替代胆固醇作为脂质体膜材可使雷公藤红素具有较好的TNBC靶向性，其药效相比胆固醇作为膜材显著增强，值得进一步研究。

Objective Based on the characteristics that triple negative breast cancer (TNBC) cells overexpress glucose transporter type 1 (Glut1) and the glucose moiety of ginsenoside Rg₃ (Rg₃) can be highly bound to Glut1 substrate, liposomes (Cel/Rg₃-LPs) loading celastrol (Cel) for TNBC thrapy were prepared with Rg₃ as menbrane materials and their targeting behaviour and anti-TNBC efficacy were investigated. Methods Cel/Rg₃-LPs was prepared by thin-film dispersion method and the prescription was optimized by single-factor experiment. The morphology, particle size, ζ potential, in vitro release and stability of the optimised Cel/Rg₃-LPs were investigated; The targeting property of Cel/Rg₃-LPs was thoroughly assessed by conducting uptake experiments with mouse 4T1 cells in vitro, as well as evaluating its therapeutic effect on BALB/c orthotopic 4T1 tumor-bearing mice. Results The optimized formulation of Cel/Rg₃-LPs comprised Cel 1.5 mg, ginsenoside Rg₃ 3.0 mg, and soybean lecithin 21.0 mg. The liposomes prepared at a hydration temperature of 50 ℃ and exhibited a spherical morphology and uniform dispersion. The mean particle size and polydispersity index (PDI) were (148.4 ± 0.23) nm and 0.19 ± 0.01, respectively, while the ζ potential was (−29.7 ± 0.34) mV. The encapsulation efficiency of celastrol in liposomes was (96.69 ± 0.03)%, and the drug loading capacity was (5.62 ± 0.01)%. Cel/Rg₃-LPs demonstrated significantly enhanced cellular uptake in 4T1 cells and significantly inhibited their proliferation. In vivo experiments using 4T1 orthotopic tumor-bearing mice indicated that Cel/Rg₃-LPs could reduce tumor tissue lipids, significantly inhibit tumor growth, exhibit good tumor targeting, and exhibit no apparent liver, kidney, or tissue toxicity. Conclusion Substituting Rg₃ for cholesterol as the liposomal membrane material improved the targeting efficacy of Cel to TNBC. The efficacy was significantly enhanced compared to using cholesterol as the membrane material, indicating the potential of Rg₃ liposomes for further research.

R283.6

国家级大学生创新创业训练计划（202310344051）；浙江省自然科学基金项目（LZ22H290001）；浙江省中医药科技项目（2023ZL362）