Characterizing EPR-mediated passive drug targeting using contrast-enhanced functional ultrasound imaging

JOURNAL OF CONTROLLED RELEASE

卷:182

Article

Theek, Benjamin^1,2  Gremse, Felix^1,2  Kunjachan, Sijumon^1,2  Fokong, Stanley¹  Pola, Robert³  Pechar, Michal³  Deckers, Roel⁴  Storm, Gert^5,6  Ehling, Josef^1,2  Kiessling, Fabian^1,2  Lammers, Twan^1,2,5,6 

[1] Rhein Westfal TH Aachen, Univ Clin, Dept Expt Mol Imaging, Aachen, Germany

[2] Rhein Westfal TH Aachen, Helmholtz Inst Biomed Engn, Aachen, Germany

[3] Acad Sci Czech Republ, Inst Macromol Chem, Prague, Czech Republic

[4] Univ Med Ctr Utrecht, Imaging Sci Inst, Utrecht, Netherlands

[5] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, Utrecht, Netherlands

[6] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Controlled Drug Delivery, NL-7500 AE Enschede, Netherlands

关键词: Drug targeting;    Nanomedicine;    Theranostics;    Cancer;    EPR;    HPMA;   

DOI  :  10.1016/j.jconrel.2014.03.007

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free