Smart Human-Serum-Albumin-As2 O3 Nanodrug with Self-Amplified Folate Receptor-Targeting Ability for Chronic Myeloid Leukemia Treatment.

ABSTRACT: Arsenic trioxide (ATO, As2 O3 ) is currently used to treat acute promyelocytic leukemia. However, expanding its use to include high-dose treatment of other cancers is severely hampered by serious side effects on healthy organs. To address these limitations, we loaded ATO onto folate (FA)-labeled human serum albumin (HSA) pretreated with glutathione (GSH) based on the low pH- and GSH-sensitive arsenic-sulfur bond, and we termed the resulting smart nanodrug as FA-HSA-ATO. FA-HSA-ATO could specifically recognize folate receptor-?-positive (FR?+) chronic myeloid leukemia (CML) cells, resulting in more intracellular accumulation of ATO. Furthermore, the nanodrug could upregulate FR? expression in CML cancer cells and xenograft tumor model, facilitating even more recruitment and uptake of FR?-targeting drugs. In?vitro and in?vivo experiments indicate that the nanodrug significantly alleviates side effects and improves therapeutic efficacy of ATO on CML and xenograft tumor model.

SUBMITTER: Peng Y 

PROVIDER: S-EPMC5912668 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature