引用

有丝分裂原活化蛋白激酶(MAPKs)是癌症发生和转移的重要信号通路之一。炭疽杆菌致死毒素(LT)是一种有效的MAPK信号抑制剂。这种毒素由两个不同的结构域组成，致命因子(LF)， MAPK抑制剂和保护抗原(PA)。为了进入各种细胞系，LF必须与保护抗原(PA)结合，从而促进LF的传递。在目前的研究中，为了阻断MAPK信号，LF被装载到抗cd19免疫脂质体纳米颗粒中，并将货物运送到Raji B细胞。脂质体纳米颗粒采用传统的脂膜形成方法制备，然后与抗cd19 VHH结合。采用流式细胞术检测结合效率。通过BrdU淋巴增殖试验证实了LF免疫脂质体的靶向细胞毒性。随后采用Real-Time PCR方法评估制剂对促凋亡基因的影响。western blot证实了LF对MAPK信号的抑制作用。对脂质体纳米配方进行优化，以达到最大的LF包封和靶向给药效果。 Next, phosphorylation of MAPK pathway mediators like MEK1/2, P38 and JNK were inhibited following the treatment of Raji cells with LF-immunoliposome. The treatment also upregulated caspase genes, clearly illustrating cell death induced by LF through pyroptosis and caspase-dependent apoptosis.In conclusion, anti-CD19 VHH immunoliposome was loaded with LF, a potent MAPK inhibitor targeting B cells, which curbs proliferation and ushers B cells toward apoptosis. Thus, immunoliposome presents as a versatile nanoparticle for delivery of LF to block aberrant MAPK activation. To use LF as a therapy, it would be necessary to materialize LF without PA. In the current study, PA was substituted with anti-CD19 immunoliposome to make it targeted to CD19+ while keeping the normal cells intact.