Spherical horse in a vacuum or applicable micelles? Behavior and shape of nanoparticles: anticancer drug carriers in real blood environment

我们希望从两个方面来突破对抗癌药物载体在真实血液环境中的行为的理解：(i)注射入血液后的大量稀释；（ii）与血液成分（如蛋白质）的特异性和非特异性相互作用。在这一点上，我们遵循对比和标记方法。正在研究的药物载体是基于临床相关的N-（2-羟丙基）甲基丙烯酰胺随机共聚物，它既携带一种抗癌药物，即阿霉素，也携带一种疏水靶向基团，如胆固醇。为了解决极端稀释下的行为，聚合物将被荧光标记，荧光相关光谱以及荧光寿命成像共聚焦显微镜将被应用，这可以确定临界胶束浓度以及胶束聚集行为。用小角中子散射（SANS）对部分氘化聚合物和小角x射线散射（SAXS）以及异常x射线散射（ASAXS，对重金属标记的聚合物）研究血浆中的胶束与蛋白质的相互作用。通过这种方式获得的详细信息与项目合作伙伴开展的生物学研究将进一步了解药物传递机制，并有助于提高载体的效率。该项目是在GACR和DFG谅解备忘录的框架内实现的。

We wish to make a breakthrough in understanding the behavior of anticancer drug carriers in real blood environment by focusing on two aspects: (i) the considerable dilution after injection into the blood and (ii) specific and nonspecific interactions with blood components, e.g. proteins. At this, we follow the contrasting and labeling approach. The drug carrier under investigation is based on clinically relevant random copolymers from N-(2-hydroxypropyl)methacrylamide) and which carry both a cancer drug, namely doxorubicin, and a hydrophobic targeting group, e.g. cholesterol. To address the behavior at extreme dilution, polymers will be fluorescence-labeled and fluorescence correlation spectroscopy as well as fluorescence-lifetime imaging confocal microscopy will be applied, which allows determination of the critical micelle concentration as well as the aggregation behavior into micelles just above. The interaction of the micelles with proteins will be addressed by studying the micelles in blood plasma using small-angle neutron scattering (SANS) on partially deuterated polymers and small-angle X-ray scattering (SAXS) as well as anomalous SAXS (ASAXS, on polymers labeled with heavy metals). The detailed information obtained this way together with the biological studies carried out by the project partner will further the understanding of the drug delivery mechanism and help to improve the efficiency of the carrier. The project is realized in the framework of the Memorandum of Understanding of the GACR and DFG.