The pathways for nanoparticle transport across tumour endothelium

IF 38.1 1区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY
Jamie L. Y. Wu, Qin Ji, Colin Blackadar, Luan N. M. Nguyen, Zachary P. Lin, Zahra Sepahi, Benjamin P. Stordy, Adrian Granda Farias, Shrey Sindhwani, Wayne Ngo, Katherine Chan, Andrea Habsid, Jason Moffat, Warren C. W. Chan
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引用次数: 0

Abstract

The active transport and retention principle is an alternative mechanism to the enhanced permeability and retention effect for explaining nanoparticle tumour delivery. It postulates that nanoparticles actively transport across tumour endothelial cells instead of passively moving through gaps between these cells. How nanoparticles transport across tumour endothelial cells remains unknown. Here we show that nanoparticles cross tumour endothelial cells predominantly using the non-receptor-based macropinocytosis pathway. We discovered that tumour endothelial cell membrane ruffles capture circulating nanoparticles, internalize them in intracellular vesicles and release them into the tumour interstitium. Tumour endothelial cells have a higher membrane ruffle density than healthy endothelium, which may partially explain the elevated nanoparticle tumour accumulation. Receptor-based endocytosis pathways such as clathrin-mediated endocytosis contribute to nanoparticle transport to a lesser extent. Nanoparticle size determines the degree of contribution for each pathway. Elucidating the nanoparticle transport mechanism is crucial for developing strategies to control nanoparticle tumour delivery.

Abstract Image

纳米颗粒在肿瘤内皮中的转运途径
主动运输和保留原理是解释纳米颗粒肿瘤递送的增强渗透性和保留效应的另一种机制。它假设纳米颗粒主动地穿过肿瘤内皮细胞,而不是被动地穿过这些细胞之间的间隙。纳米颗粒如何在肿瘤内皮细胞间运输尚不清楚。在这里,我们发现纳米颗粒主要通过非受体为基础的巨噬细胞途径穿过肿瘤内皮细胞。我们发现,肿瘤内皮细胞的膜褶捕获循环的纳米颗粒,将其内化在细胞内囊泡中,并将其释放到肿瘤间质中。肿瘤内皮细胞比健康内皮细胞具有更高的膜皱褶密度,这可能部分解释了纳米颗粒肿瘤积聚的增加。基于受体的内吞途径,如网格蛋白介导的内吞作用,在较小程度上有助于纳米颗粒的运输。纳米颗粒的大小决定了每种途径的贡献程度。阐明纳米颗粒的输送机制对于制定控制纳米颗粒肿瘤输送的策略至关重要。
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来源期刊
Nature nanotechnology
Nature nanotechnology 工程技术-材料科学:综合
CiteScore
59.70
自引率
0.80%
发文量
196
审稿时长
4-8 weeks
期刊介绍: Nature Nanotechnology is a prestigious journal that publishes high-quality papers in various areas of nanoscience and nanotechnology. The journal focuses on the design, characterization, and production of structures, devices, and systems that manipulate and control materials at atomic, molecular, and macromolecular scales. It encompasses both bottom-up and top-down approaches, as well as their combinations. Furthermore, Nature Nanotechnology fosters the exchange of ideas among researchers from diverse disciplines such as chemistry, physics, material science, biomedical research, engineering, and more. It promotes collaboration at the forefront of this multidisciplinary field. The journal covers a wide range of topics, from fundamental research in physics, chemistry, and biology, including computational work and simulations, to the development of innovative devices and technologies for various industrial sectors such as information technology, medicine, manufacturing, high-performance materials, energy, and environmental technologies. It includes coverage of organic, inorganic, and hybrid materials.
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