Image-guided, targeted and triggered drug delivery to tumors using polymer-based microbubbles

JOURNAL OF CONTROLLED RELEASE

卷:163

Article; Proceedings Paper

Fokong, Stanley^1,2  Theek, Benjamin^1,2  Wu, Zhuojun^1,2,3  Koczera, Patrick^1,2  Appold, Lia^1,2  Jorge, Samuel^1,2  Resch-Genger, Ute⁴  van Zandvoort, Marc^3,5  Storm, Gert^6,7  Kiessling, Fabian^1,2  Lammers, Twan^1,2,6,7 

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

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

[3] Rhein Westfal TH Aachen, Univ Clin, Inst Mol Cardiol, Aachen, Germany

[4] BAM Fed Inst Mat Res & Testing, Div Biophoton, Berlin, Germany

[5] Maastricht Univ, Med Ctr, Dept Biomed Engn, Maastricht, Netherlands

[6] Univ Utrecht, Dept Pharmaceut, Utrecht, Netherlands

[7] Univ Twente, MIRA Inst Biomed Technol & Tech Med, Dept Targeted Therapeut, NL-7500 AE Enschede, Netherlands

关键词: Ultrasound;    Microbubbles;    Fluorescent reporter;    Drug delivery;    Tumor targeting;    Theranostics;   

DOI  :  10.1016/j.jconrel.2012.05.007

来源: Elsevier

【 摘 要 】

Microbubbles (MB) are routinely used contrast agents for functional and molecular ultrasound (US) imaging. In addition, they have been attracting more and more attention for drug delivery purposes, enabling e. g. US-mediated drug delivery across biological barriers and US-induced triggered drug release from the MB shell. The vast majority of efforts in this regard have thus far focused on phospholipid-based soft-shell MB, which are suboptimal for stably incorporating large amounts of drug molecules because of their relatively thin shell. Using poly(butyl cyanoacrylate) (PBCA)-based hard-shell MB, we show here that both hydrophilic (Rhodamine-B) and hydrophobic (Coumarin-6) model drugs can be efficiently and stably entrapped within the similar to 50 nm shell of PBCA MB. In addition, we demonstrate that model drug loading does not negatively affect the acoustic properties of the MB, and that functionalizing the surface of fluorophore-loaded MB with anti-VEGFR2 antibodies enables image-guided and targeted model drug delivery to tumor blood vessels. Finally, we show both in vitro and in vivo that disintegrating VEGFR2-targeted MB with high-mechanical index US pulses leads to high levels of model drug release. Consequently, these findings indicate that polymer-based MB are highly suitable systems for image-guided, targeted and triggered drug delivery to tumors and tumor blood vessels. (C) 2012 Elsevier B.V. All rights reserved.

【 授权许可】

Free