ArticleMedical oncology (Northwood, London, England)2026
Targeted delivery of venetoclax-encapsulated human heavy chain ferritin nanoparticles in acute myeloid leukemia.
Article in Medical oncology (Northwood, London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Venetoclax (VEN) is a B-cell lymphoma 2 (BCL-2) inhibitor approved for treatment in acute myeloid leukemia (AML). Human heavy chain ferritin (HFn) is a bio-inspired nanoparticle (NP) utilized to deliver multiple chemotherapies to tumor cells through CD71-mediated endocytosis. In this study, the efficacy of VEN/HFn NP was investigated for targeted delivery in AML. Recombinant HFn was expressed, purified, and characterized using SDS-PAGE, western blotting, and dynamic light scattering (DLS). VEN was encapsulated in HFn, and the resulting VEN/HFn NPs, along with the corresponding controls, were utilized to treat the AML cell lines THP-1 and K562. Cell proliferation, apoptosis, and CD71 and HLA-I expression levels were assessed using MTT and flow cytometry assays. The mRNA expression of IFN-β and BCL-2 was measured using Real-time PCR. Drug-nanoparticle interactions were analyzed using molecular docking. HFn NPs were successfully constructed with a 95% VEN encapsulation efficiency, supported by molecular docking simulations that indicated a strong binding affinity (-9.2 kcal/mol) and a thermodynamically stable complex. Functionally, both VEN/HFn and free VEN treatments significantly induced apoptosis and upregulated HLA-I and IFN-β expression in both cell lines. Also, BCL-2 expression was significantly reduced. Importantly, no significant differences in these effects were observed between the VEN/HFn and free VEN, confirming that encapsulation preserves the drug's activity. Our results indicate a promising and efficient strategy for the encapsulation and targeted delivery of venetoclax using HFn nanoparticles for AML patients. This delivery system can support co-delivery of various drugs and combination therapy of tumor cells.
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