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

点击翻译按钮获取中文摘要

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.