Bixner Oliver, Gal Noga, Zaba Christoph, Scheberl Andrea, Reimhult Erik
Institute for Biologically Inspired Materials, Department of Nanobiotechnology, University of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria.
Institute for Synthetic Bioarchitectures, Department of Nanobiotechnology, University of Natural Resources and Life Sciences, Muthgasse 11, 1190 Vienna, Austria.
Materials (Basel). 2017 Nov 13;10(11):1303. doi: 10.3390/ma10111303.
We present a potential theranostic delivery platform based on the amphiphilic diblock copolymer polybutadiene--poly (ethylene oxide) combining covalent fluorescent labeling and membrane incorporation of superparamagnetic iron oxide nanoparticles for multimodal imaging. A simple self-assembly and labeling approach to create the fluorescent and magnetic vesicles is described. Cell uptake of the densely PEGylated polymer vesicles could be altered by surface modifications that vary surface charge and accessibility of the membrane active species. Cell uptake and cytotoxicity were evaluated by confocal microscopy, transmission electron microscopy, iron content and metabolic assays, utilizing multimodal tracking of membrane fluorophores and nanoparticles. Cationic functionalization of vesicles promoted endocytotic uptake. In particular, incorporation of cationic lipids in the polymersome membrane yielded tremendously increased uptake of polymersomes and magnetopolymersomes without increase in cytotoxicity. Ultrastructure investigations showed that cationic magnetopolymersomes disintegrated upon hydrolysis, including the dissolution of incorporated iron oxide nanoparticles. The presented platform could find future use in theranostic multimodal imaging and magnetically triggered delivery by incorporation of thermorepsonsive amphiphiles that can break the membrane integrity upon magnetic heating via the embedded superparamagnetic nanoparticles.
我们展示了一种基于两亲性二嵌段共聚物聚丁二烯-聚(环氧乙烷)的潜在诊疗递送平台,该平台结合了共价荧光标记和超顺磁性氧化铁纳米颗粒的膜包封,用于多模态成像。描述了一种创建荧光和磁性囊泡的简单自组装和标记方法。通过改变膜活性物质的表面电荷和可及性的表面修饰,可以改变高度聚乙二醇化聚合物囊泡的细胞摄取。利用膜荧光团和纳米颗粒的多模态追踪,通过共聚焦显微镜、透射电子显微镜、铁含量和代谢分析评估细胞摄取和细胞毒性。囊泡的阳离子功能化促进了内吞摄取。特别地,在聚合物囊泡膜中掺入阳离子脂质可极大地增加聚合物囊泡和磁性聚合物囊泡的摄取,而不会增加细胞毒性。超微结构研究表明,阳离子磁性聚合物囊泡在水解时会解体,包括掺入的氧化铁纳米颗粒的溶解。通过掺入热响应性两亲物,该平台未来可用于诊疗多模态成像和磁触发递送,热响应性两亲物可通过嵌入的超顺磁性纳米颗粒在磁加热时破坏膜完整性。