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研制CD123单抗修饰的载丹参酮Ⅱ_A免疫脂质体(CD123-TanⅡ_A-ILP),以期实现对白血病细胞的主动靶向给药。采用正交试验法优化脂质体处方,薄膜分散-探头超声法制备载丹参酮Ⅱ_A长循环脂质体(TanⅡ_A-LP),以后插入法得到CD123-TanⅡ_A-ILP。流式细胞术检测NB4细胞对脂质体的摄取率,改良MTT法检测CD123-TanⅡ_A-ILP对NB4细胞的增殖抑制作用。研究结果表明,NB4细胞对CD123单抗修饰的免疫脂质体的摄取显著高于对游离药物及其载药脂质体的摄取;TanⅡ_A,TanⅡ_A-LP和CD123-TanⅡ_A-ILP与NB4细胞共培养48 h,其IC_(50)分别为20.87,11.71,7.17μmol·L~(-1)。CD123-ILP有望为AML的治疗提供新的靶向给药策略。
The CD123-TanⅡ_A-ILP containing CD123 mAb was modified in order to achieve active targeting of leukemia cells. Orthogonal test was used to optimize the formulation of liposomes and thin-film dispersion-probe ultrasound to prepare TanⅡ_A-LP containing liposomes. Afterwards, CD123-TanⅡ_A-ILP was obtained by insert method. The uptake rate of NB4 cells to liposomes was detected by flow cytometry. The inhibitory effect of CD123-TanⅡ_A-ILP on the proliferation of NB4 cells was detected by MTT assay. The results showed that uptake of CD123 mAb by NB4 cells was significantly higher than that of free drug and drug-loaded liposomes. TanⅡ_A, TanⅡ_A-LP and CD123-TanⅡ_A-ILP were co-cultured with NB4 cells 48 h, the IC 50 (50) were 20.87,11.71,7.17μmol·L -1. CD123-ILP is expected to provide a new targeted drug delivery strategy for the treatment of AML.