Anti-CD19 mAb-conjugated human serum albumin nanoparticles effectively deliver doxorubicin to B-lymphoblastic leukemia cells.

Abstract

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 IC50 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.