Scholarlink

<p>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&#xa0;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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Targeted delivery of venetoclax-encapsulated human heavy chain ferritin nanoparticles in acute myeloid leukemia

  • 期刊论文

  • 发表日期：

    2026年2月5日

查看全文
  • Mohadeseh Khodaverdian,
  • Misagh Rajabinejad,
  • Reza Valadan,
  • Majid Saeedi,
  • Reza Negarandeh,
  • Hadi Hossein-Nataj,
  • Ramin Shekarriz,
  • Hossein Asgarian-Omran

摘要

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.