Koczera Patrick, Appold Lia, Shi Yang, Liu Mengjiao, Dasgupta Anshuman, Pathak Vertika, Ojha Tarun, Fokong Stanley, Wu Zhuojun, van Zandvoort Marc, Iranzo Olga, Kuehne Alexander J C, Pich Andrij, Kiessling Fabian, Lammers Twan
Department of Experimental Molecular Imaging (ExMI), Helmholtz Institute for Biomedical Engineering, University Hospital RWTH, Pauwelsstr. 30, 52074 Aachen, Germany; Department of Intensive Care, University Hospital RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
Department of Experimental Molecular Imaging (ExMI), Helmholtz Institute for Biomedical Engineering, University Hospital RWTH, Pauwelsstr. 30, 52074 Aachen, Germany.
J Control Release. 2017 Aug 10;259:128-135. doi: 10.1016/j.jconrel.2017.03.006. Epub 2017 Mar 6.
Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated drug delivery. Molecular imaging of angiogenic tumor blood vessels and inflamed atherosclerotic endothelium is performed by modifying the surface of PBCA MB with peptides and antibodies recognizing E-selectin and VCAM-1. Stable and inertial cavitation of PBCA MB enables sonoporation and permeabilization of blood vessels in tumors and in the brain, which can be employed for direct and indirect drug delivery. Direct drug delivery is based on US-induced release of (model) drug molecules from the MB shell. Indirect drug delivery refers to US- and MB-mediated enhancement of extravasation and penetration of co-administered drugs and drug delivery systems. These findings are in line with recently reported pioneering proof-of-principle studies showing the usefulness of (phospholipid) MB for molecular US imaging and sonoporation-enhanced drug delivery in patients. They aim to exemplify the potential and the broad applicability of combining MB with US to improve disease diagnosis and therapy.
微泡（MB）通常用作超声（US）成像的造影剂。我们描述了不同类型的靶向和载药聚氰基丙烯酸正丁酯（PBCA）微泡，并证明了它们适用于多种生物医学应用，包括分子超声成像和超声介导的药物递送。通过用识别E-选择素和血管细胞黏附分子-1（VCAM-1）的肽和抗体修饰PBCA微泡的表面，对血管生成性肿瘤血管和炎症性动脉粥样硬化内皮进行分子成像。PBCA微泡的稳定空化和惯性空化能够实现肿瘤和大脑中血管的声孔形成和通透化，可用于直接和间接药物递送。直接药物递送基于超声诱导（模型）药物分子从微泡壳中释放。间接药物递送是指超声和微泡介导的共同给药药物和药物递送系统的血管外渗和渗透增强。这些发现与最近报道的开创性原理验证研究一致，这些研究表明（磷脂）微泡在患者分子超声成像和声孔形成增强药物递送中的有用性。它们旨在举例说明将微泡与超声相结合以改善疾病诊断和治疗的潜力和广泛适用性。
