School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin.
The Second Hospital of Dalian Medical University, Dalian, China.
Pharmazie. 2020 Jul 1;75(7):318-323. doi: 10.1691/ph.2020.0026.
B-Lymphoblastic leukemia (B-LL) is the most common childhood hematological malignancy. Although its overall prognosis is good, the outcome after relapse is poor. CD19 is highly expressed on the membrane of most malignant B-cells, and was shown to be a promising therapeutic target of B-LL. In this present work, we designed and synthesized a novel drug carrier, anti-CD19 monoclonal antibody-conjugated human serum albumin nanoparticles (HSA-CD19 NPs). Doxorubicin (DOX) was well encapsulated into the HSA-CD19 NPs to form an anticancer nanodrug DOX/HSA-CD19. DOX/HSA-CD19 was preferentially uptaken by CD19 B-LL cell line KOPN-8. DOX/HSA-CD19 showed strong antiproliferative effect on KOPN-8 cells with an IC value of 4.1 μg/mL. Further, proapoptotic Bax and caspase-3 were significantly elevated, but antiapoptotic Bcl2 was reduced in DOX/HSA-CD19 treated KOPN-8 cells, indicating the activation of the apoptosis pathway by the nanodrug. By contrast, DOX/HSA-CD19 did not show affinity to CD19-monocytic cell line, U937, and did not affect its proliferation. Collectively, HSA-CD19 NPs are a kind of effective novel drug carrier, and DOX/HSA-CD19 is a promising antitumor nanodrug for the treatment of B-LL.
B 细胞淋巴母细胞白血病(B-LL)是最常见的儿童血液系统恶性肿瘤。尽管其整体预后良好,但复发后的结果较差。CD19 在大多数恶性 B 细胞的膜上高度表达,被证明是 B-LL 的有前途的治疗靶点。在本研究中,我们设计并合成了一种新型药物载体,抗 CD19 单克隆抗体偶联人血清白蛋白纳米颗粒(HSA-CD19 NPs)。阿霉素(DOX)被很好地包裹在 HSA-CD19 NPs 中,形成一种抗癌纳米药物 DOX/HSA-CD19。DOX/HSA-CD19 优先被 CD19 B-LL 细胞系 KOPN-8 摄取。DOX/HSA-CD19 对 KOPN-8 细胞表现出强烈的增殖抑制作用,IC 值为 4.1μg/mL。此外,促凋亡 Bax 和 caspase-3 明显升高,而抗凋亡 Bcl2 降低,表明纳米药物激活了凋亡途径。相比之下,DOX/HSA-CD19 对 CD19-单核细胞系 U937 没有亲和力,也不影响其增殖。总之,HSA-CD19 NPs 是一种有效的新型药物载体,而 DOX/HSA-CD19 是治疗 B-LL 的一种有前途的抗肿瘤纳米药物。