期刊
JOURNAL OF CONTROLLED RELEASE
卷 182, 期 -, 页码 83-89出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2014.03.007
关键词
Drug targeting; Nanomedicine; Theranostics; Cancer; EPR; HPMA
资金
- European Research Council [ERC-StG-309495]
- DFG [LA 2937/1-2]
- European Union (European Regional Development Fund-Investing In Your Future)
- COST-Action [TD1004]
- North Rhine Westphalia (HighTech. NRW/EUZiel 2-Programm (EFRE)
- ForSaTum)
- Grant Agency of the Czech Republic [P207/12/J030]
- Philips Research
The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a similar to 10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularizationwas correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5 to 12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4 to 11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, within the case of reconstructed CT-FMT, correlation coefficients of similar to 0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-select patients likely to respond to passively tumor-targeted nanomedicine treatments. (C) 2014 Elsevier B. V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据