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

真空中的球形马或适用的胶束？

• 批准号: 265795383
• 负责人: Professorin Dr. Christine M. Papadakis
• 金额: --
• 依托单位: Ústav makromolekulární chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/265795383?language=en
• 关键词: Spherical; horse; vacuum; applicable; micelles

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.

我们希望通过关注两个方面来在理解抗癌药物载体在真实的血液环境中的行为方面取得突破：（i）注射到血液中后的相当大的稀释和（ii）与血液组分（例如蛋白质）的特异性和非特异性相互作用。在这一点上，我们遵循对比和标签的方法。研究中的药物载体基于来自N-（2-羟丙基）甲基丙烯酰胺的临床相关无规共聚物，并且其携带癌症药物（即阿霉素）和疏水靶向基团（例如胆固醇）。为了解决极端稀释时的行为，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，这允许确定临界胶束浓度以及聚集成胶束的行为。胶束与蛋白质的相互作用将通过使用小角中子散射（SANS）在部分氘代聚合物和小角X射线散射（SAXS）以及异常SAXS（ASAXS，标记有重金属的聚合物）研究血浆中的胶束来解决。通过这种方式获得的详细信息以及项目合作伙伴进行的生物学研究将进一步了解药物输送机制，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施的。

项目成果

Binding of HSA to Macromolecular pHPMA Based Nanoparticles for Drug Delivery: An Investigation Using Fluorescence Methods.

• DOI: 10.1021/acs.langmuir.8b01015
• 发表时间: 2018-06
• 期刊: Langmuir : the ACS journal of surfaces and colloids
• 作者: Xiaohan Zhang;P. Chytil;T. Etrych;Weiwei Liu;Letícia Rodrigues;G. Winter;S. Filippov;C. Papadakis-C.-Papa

Influence of molar mass, dispersity, and type and location of hydrophobic side chain moieties on the critical micellar concentration and stability of amphiphilic HPMA-based polymer drug carriers

• DOI: 10.1007/s00396-017-4027-7
• 发表时间: 2017-08-01
• 期刊: COLLOID AND POLYMER SCIENCE
• 影响因子: 2.4
• 作者: Filippov, Sergey K.;Vishnevetskaya, Natalya S.;Papadakis, Christine M.
• 通讯作者: Papadakis, Christine M.