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Size-Dependent EPR Effect of Polymeric Nanoparticles on Tumor Targeting.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2019-12-03 , DOI: 10.1002/adhm.201901223
Homan Kang 1 , Sunghoon Rho 1 , Wesley R Stiles 1 , Shuang Hu 1 , Yoonji Baek 1 , Do Won Hwang 1 , Satoshi Kashiwagi 1 , Moon Suk Kim 2 , Hak Soo Choi 1
Affiliation  

Passive targeting of large nanoparticles by the enhanced permeability and retention (EPR) effect is a crucial concept for solid tumor targeting in cancer nanomedicine. There is, however, a trade-off between the long-term blood circulation of nanoparticles and their nonspecific background tissue uptake. To define this size-dependent EPR effect, near-infrared fluorophore-conjugated polyethylene glycols (PEG-ZW800s; 1-60 kDa) are designed and their biodistribution, pharmacokinetics, and renal clearance are evaluated in tumor-bearing mice. The targeting efficiency of size-variant PEG-ZW800s is investigated in terms of tumor-to-background ratio (TBR). Interestingly, smaller sized PEGs (≤20 kDa, 12 nm) exhibit significant tumor targeting with minimum to no nonspecific uptakes, while larger sized PEGs (>20 kDa, 13 nm) accumulate highly in major organs, including the lungs, liver, and pancreas. Among those tested, 20 kDa PEG-ZW800 exhibits the highest TBR, while excreting unbound molecules to the urinary bladder. This result lays a foundation for engineering tumor-targeted nanoparticles and therapeutics based on the size-dependent EPR effect.

中文翻译:

聚合物纳米粒子对肿瘤靶向的大小依赖性EPR效应。

通过增强的渗透性和保留(EPR)效应被动靶向大型纳米颗粒是癌症纳米医学中实体肿瘤靶向的关键概念。但是,在纳米颗粒的长期血液循环与非特异性背景组织摄取之间需要权衡。为了定义这种依赖于大小的EPR效应,设计了近红外荧光团缀合的聚乙二醇(PEG-ZW800s; 1-60 kDa),并在荷瘤小鼠中评估了它们的生物分布,药代动力学和肾清除率。根据肿瘤与背景的比率(TBR)研究了大小可变的PEG-ZW800s的靶向效率。有趣的是,较小尺寸的PEG(≤20kDa,12 nm)表现出显着的肿瘤靶向性,具有最小或无非特异性摄取,而较大尺寸的PEG(> 20 kDa,13 nm)在主要器官中高度积聚,包括肺,肝和胰腺。在这些测试中,20 kDa PEG-ZW800表现出最高的TBR,同时将未结合的分子排泄到膀胱中。该结果为基于大小依赖的EPR效应工程靶向肿瘤的纳米颗粒和治疗剂奠定了基础。
更新日期:2020-01-08
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