Dual-Targeted Drug Delivery to Myeloid Leukemia Cells via Complement- and Transferrin-Based Protein Corona

IF 9.6 1区材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Letters Pub Date : 2024-12-18 DOI:10.1021/acs.nanolett.4c04429

Wen Wu, Yuanyuan Li, Qihui Liu, Tao Liu, Yanan Zhao, Hui Shao, Ping Ren, Yueyang Tang, Jiayi Feng, Yihan Wang, Guodong Sun, Haiyan Liu, Yuansong Bai, Fangfang Chen

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Abstract

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. In vitro, 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%. In vivo, the distribution of NAPs correlated to the organ infiltration pattern of leukemic cells. NAPs demonstrated antileukemic activity in both in vitro and in vivo 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.

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尽管蛋白质电晕在传统上被认为是一种障碍，但它却能促进靶向给药系统的发展。本研究提出了一种利用具有凝集蛋白的纳米颗粒（NAPs）靶向治疗急性髓性白血病（AML）的创新方法。NAPs 中凝集的转铁蛋白和 C3b 可选择性地与 CD71 和 CD11b 结合，与非恶性细胞相比，这些受体在骨髓性白血病细胞上过度表达。在体外，NAPs 在白血病细胞中的多柔比星（DOX）吸收率为 73.9%，而游离药物的吸收率仅为 6.19%，同时在正常细胞中的脱靶累积率从 42.9% 显著降至 5.76%。在体内，NAPs 的分布与白血病细胞的器官浸润模式相关。NAPs 在体外和体内的 NSG 小鼠模型中都表现出了抗白血病活性，可通过细胞凋亡和铁变态诱导细胞死亡。总之，NAP介导的靶向给药是治疗急性髓细胞白血病的一种很有前景的治疗策略，它能提高疗效并最大限度地减少脱靶效应。

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来源期刊

Nano Letters 工程技术-材料科学：综合

CiteScore

16.80

自引率

2.80%

发文量

1182

审稿时长

1.4 months

期刊介绍： Nano Letters serves as a dynamic platform for promptly disseminating original results in fundamental, applied, and emerging research across all facets of nanoscience and nanotechnology. A pivotal criterion for inclusion within Nano Letters is the convergence of at least two different areas or disciplines, ensuring a rich interdisciplinary scope. The journal is dedicated to fostering exploration in diverse areas, including: - Experimental and theoretical findings on physical, chemical, and biological phenomena at the nanoscale - Synthesis, characterization, and processing of organic, inorganic, polymer, and hybrid nanomaterials through physical, chemical, and biological methodologies - Modeling and simulation of synthetic, assembly, and interaction processes - Realization of integrated nanostructures and nano-engineered devices exhibiting advanced performance - Applications of nanoscale materials in living and environmental systems Nano Letters is committed to advancing and showcasing groundbreaking research that intersects various domains, fostering innovation and collaboration in the ever-evolving field of nanoscience and nanotechnology.