Background: Acute myeloid leukemia (AML) is a hematological malignant tumor. The common chemotherapy results in various side-effect and drug-resistance for AML, so it is urgent to find a non-toxic natural… Click to show full abstract
Background: Acute myeloid leukemia (AML) is a hematological malignant tumor. The common chemotherapy results in various side-effect and drug-resistance for AML, so it is urgent to find a non-toxic natural drug for AML therapy. Herein, for the first time, the Se nanoparticles embedded in nanotube consisted of triple helix β-D-glucan (BFP) exhibit the high anti-leukemia effects. Methods: A triple helix β-(1, 3)-D-glucan (BFP) extracted from the black fungus was self-assembled into nanotube in water, and Se nanoparticles (SeNPs) were wrapped to form stable inclusion complex BFP-Se. The CCK8 assays, lactose dehydrogenase release assays, optofluidics chips and flow cytometry were used to test the anti-leukemia effects of BFP-Se in vitro and in vivo. Results: The SeNPs embedded in the BFP nanotubes exhibited high stability in water, avoiding aggregation and dispersion to out. In vitro, the BFP-Se significantly inhibited the proliferation of AML cell lines and patient cells and markedly increased the cytotoxicity on AML cells. BFP-Se slowed the Molm-13 GFP+ cells growth. On single-cell levels, the U937 cells were gradually swelled and lysed with BFP-Se treatment. In addition, BFP-Se had little toxic to hematopoietic stem cells (HSC) and T cells compared to Ara-c. Flow cytometry indicated that BFP-Se promoted the cell apoptosis and blocked cell cycle of AML cells. Further, after injection of BFP-Se, the survival was longer on AML PDX model constructed with B-NSG mice. The blood and bone marrow analysis indicated the anti-leukemia effects of BFP-Se in vivo. Moreover, BFP-Se extremely increased the total antioxidant capacity (T-AOC) of AML cells, and decreased the expression of c-Jun activation domain-binding protein-1 (Jab1) and thioredoxin 1 (Trx1). Conclusion: This biocompatible polysaccharide nanotube containing Se nanoparticles - against AML would provide a novel strategy for AML therapy. Citation Format: Yanxia Jin, Liqin Cai, Qian Yang, Ziyi Luo, Lina Zhang, Fuling Zhou. Anti-leukemia activities of selenium nanoparticles embedded in nanotube consisted of triple-helix β-D-glucan [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 586.
               
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