Prussian Blue Nanozyme Potentiates Venetoclax Efficacy in Acute Myeloid Leukemia by Inducing a More Mature Phenotype.
| Title: | Prussian Blue Nanozyme Potentiates Venetoclax Efficacy in Acute Myeloid Leukemia by Inducing a More Mature Phenotype. |
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| Authors: | Yang F; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Wu H; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Yao J; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Peng X; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Yang A; Translational Medicine Laboratory, Beijing Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, People's Republic of China.; Wen T; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Meng J; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Liu J; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Zhang Y; State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Collaborative Innovation Center of Suzhou Nano Science and Technology, Southeast University, Nanjing, People's Republic of China.; Wang T; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Xu H; Institute of Basic Medical Sciences & School of Basic Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China.; Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, People's Republic of China. |
| Source: | International journal of nanomedicine [Int J Nanomedicine] 2026 May 25; Vol. 21, pp. 601085. Date of Electronic Publication: 2026 May 25 (Print Publication: 2026). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: DOVE Medical Press Country of Publication: New Zealand NLM ID: 101263847 Publication Model: eCollection Cited Medium: Internet ISSN: 1178-2013 (Electronic) Linking ISSN: 11769114 NLM ISO Abbreviation: Int J Nanomedicine Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Auckland : DOVE Medical Press |
| MeSH Terms: | Sulfonamides*/pharmacology ; Sulfonamides*/chemistry ; Bridged Bicyclo Compounds, Heterocyclic*/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic*/chemistry ; Leukemia, Myeloid, Acute*/drug therapy ; Leukemia, Myeloid, Acute*/pathology ; Leukemia, Myeloid, Acute*/metabolism ; Ferrocyanides*/pharmacology ; Ferrocyanides*/chemistry ; Antineoplastic Agents*/pharmacology ; Antineoplastic Agents*/chemistry ; Nanoparticles*/chemistry; Apoptosis/drug effects ; Cell Differentiation/drug effects ; Membrane Potential, Mitochondrial/drug effects ; Drug Resistance, Neoplasm/drug effects ; Animals ; Mice ; Humans ; Cell Line, Tumor ; Phenotype ; Female |
| Abstract: | Introduction: Acute Myeloid Leukemia (AML) is characterized by the clonal expansion of undifferentiated myeloid precursors and is associated with notably higher incidence and mortality rates in the elderly population. While the BCL-2 inhibitor Venetoclax has transformed the therapeutic landscape for patients with AML who were ineligible for intensive therapy, primary and acquired resistance remained major obstacles to durable responses.; Methods: In this study, an ultra-small Prussian Blue nanozyme (USPBNP)-based "maturation-priming" strategy was investigated to enhance Venetoclax sensitivity. USPBNPs were synthesized and characterized for physicochemical properties and enzyme-mimetic activities. Their differentiation-inducing effects were evaluated in Venetoclax-sensitive MOLM-13 cells, acquired-resistant RMOLM-13 cells, primary-resistant OCI-AML3 cells, murine C1498 AML cells, an AML1-ETO/KITD816V murine transplant model, and primary human AML bone marrow mononuclear cells. Cellular maturation was assessed by morphological analysis and flow-cytometric detection of lineage-associated markers. Venetoclax sensitization was evaluated by apoptosis assays, mitochondrial membrane potential analysis, and detection of apoptosis-related proteins.; Results: In vitro, USPBNPs effectively reshaped the leukemic phenotype, driving differentiation in MOLM-13, RMOLM-13, and OCI-AML3 AML cells, evidenced by the reduced nucleo-cytoplasmic ratio as well as up-regulated CD11b, CD14, CD235a and CD41a. The "maturation-priming" effects were also confirmed through cross-species models in C1498 murine AML cells and a refractory AML1-ETO/KITD816V murine transplant mice model in vivo and in human clinical specimen. This phenotypic maturation lowered the apoptotic threshold of Venetoclax, resulting in mitochondrial membrane potential collapse, Caspase-3 activation, and the down-regulation of the resistance-associated protein MCL-1.; Conclusion: These findings supported USPBNPs as a maturation-priming approach in AML models with distinct genetic backgrounds and Venetoclax resistance patterns. The combination of USPBNPs and Venetoclax coupled differentiation induction with apoptosis and might provide a potential strategy for improving Venetoclax responsiveness in AML.; (© 2026 Yang et al.) |
| Competing Interests: | The authors declare no competing interest in this work. |
| Contributed Indexing: | Keywords: acute myeloid leukemia; apoptosis; differentiation; prussian blue nanozyme; venetoclax |
| Substance Nomenclature: | 0 (Sulfonamides); 0 (Bridged Bicyclo Compounds, Heterocyclic); N54AIC43PW (venetoclax); 0 (Ferrocyanides); TLE294X33A (ferric ferrocyanide); 0 (Antineoplastic Agents) |
| Entry Date(s): | Date Created: 20260602 Date Completed: 20260603 Latest Revision: 20260603 |
| Update Code: | 20260603 |
| PubMed Central ID: | PMC13222633 |
| DOI: | 10.2147/IJN.S601085 |
| PMID: | 42226963 |
| Database: | MEDLINE |
Journal Article