Dual-Targeted Drug Delivery to Myeloid Leukemia Cells via Complement- and Transferrin-Based Protein Corona
Although traditionally regarded as an impediment, the protein corona can facilitate the advancement of targeted drug delivery systems. This study presents an innovative approach for targeting acute myeloid leukemia (AML) using nanoparticles with agglutinated protein (NAPs). Agglutinated transferrin and C3b in NAPs selectively bind to CD71 and CD11b, receptors that are overexpressed on myeloid leukemic cells compared to nonmalignant cells. <i>In vitro</i>, NAPs achieved a 73.9% doxorubicin (DOX) uptake in leukemic cells, compared to 6.19% for the free drug, while significantly reducing off-target accumulation in normal cells from 42.9% to 5.76%. <i>In vivo</i>, the distribution of NAPs correlated to the organ infiltration pattern of leukemic cells. NAPs demonstrated antileukemic activity in both <i>in vitro</i> and <i>in vivo</i> NSG mouse models, inducing cell death via apoptosis and ferroptosis. In conclusion, NAP-mediated targeted drug delivery represents a promising therapeutic strategy for AML, enhancing treatment efficacy and minimizing off-target effects.
Authors
- Guodong Sun (ORCID: https://orcid.org/0000-0001-5336-368X)
- Hui Shao (ORCID: https://orcid.org/0000-0001-7566-6921)
- Tao Liu (ORCID: https://orcid.org/0000-0001-7851-611X)
- Wu Wen
- Haiyan Liu (ORCID: https://orcid.org/0000-0001-6871-8826)
- Yihan Wang (ORCID: https://orcid.org/0000-0003-1628-5736)
- Fangfang Chen (ORCID: https://orcid.org/0000-0002-3284-3331)
- Yanan Zhao (ORCID: https://orcid.org/0000-0002-4938-9235)
- Ping Ren
- Jiayi Feng (ORCID: https://orcid.org/0009-0009-4405-9518)
- Qihui Liu (ORCID: https://orcid.org/0000-0002-8985-1906)
- Ying Tang (ORCID: https://orcid.org/0000-0002-1105-9003)
- Yuansong Bai (ORCID: https://orcid.org/0000-0002-3596-0138)
- Yuan-Yuan Li (ORCID: https://orcid.org/0009-0006-8043-8900)
Institutions
- Union Hospital (HK)
- Jinan University (CN)
- Jilin University (CN)
- First Hospital of Jilin University (CN)
- Union Hospital (CN)
- State Key Laboratory of Inorganic Synthesis and Preparative Chemistry
Publication Details
- Journal
- Nano Letters
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1021/acs.nanolett.4c04429
- Citations
- 4
- Primary Topic
- Iron Metabolism and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.82
Funders
- Natural Science Foundation of Jilin Province
- National Natural Science Foundation of China
- Jilin University
- National Key Research and Development Program of China
- Program for Jilin University Science and Technology Innovative Research Team