Polymeric Nanocarriers for the Visualization and Quantification of Molecular Release

用于分子释放可视化和定量的聚合物纳米载体

• 批准号: 265519003
• 负责人: Professor Dr. Christopher Barner-Kowollik
• 金额: --
• 依托单位: School of Chemistry and Physics
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/265519003?language=en
• 关键词: Polymeric; Nanocarriers; Visualization; Quantification; Molecular

The overarching aim of the current proposal is to develop a technology platform that can follow and quantify molecular release mechanisms (e.g. drug release) by incorporating a switchable fluorescent moiety which is able to simultaneously visualise and quantify payload delivery. The development of polymeric nanoparticles as drug delivery vehicles has facilitated effective targeted release strategies for a variety of therapeutics. When combined with imaging agents, these nanoparticles allow for the visualization of the biodistribution of a molecular payload. However, the majority of these systems do not report on the release of the drug from the carrier, an important facet which is crucial to the design of optimized payload delivery systems and will enable an in-depth understanding of biological effects. The sought project will develop novel polymeric nano-carriers which can show where, when and how much molecular payload is delivered to a specific target site. Featuring a strong polymer chemical focus, this will be achieved through the incorporation of a nitroxide-fluorophore couple into the delivery system. When a fluorophore is held in close proximity to a nitroxide, the fluorophore enters a profluorescent state and a complete quenching of the fluorescence is observed. When the load is released from the carrier - through stimuli-induced scission of a covalent linkage - separation of the nitroxide and fluorophore moieties will occur and an immediate increase in fluorescence will be observed, thereby allowing the quantification of the delivery. The molecules will be designed such that the switch on of one fluorophore will be related to the release of one delivered molecule, leading to a quantifiable measure of release. In order to realize such an ideal, a number of chemical challenges have been identified that are at the core of the current proposal and will be addressed, leading to a more profound understanding of the mechanisms by which delivery from polymeric nanocarriers is achieved. The concept will be evidenced in in vitro as well as in vivo studies to demonstrate its practical applicability.

当前建议的总体目的是开发一个技术平台，可以通过合并一个可切换的荧光部分来遵循和量化分子释放机制（例如药物释放），该部分能够同时可视化和量化有效载荷。 作为药物输送车，聚合物纳米颗粒的开发促进了各种治疗剂的有效释放策略。当与成像剂结合使用时，这些纳米颗粒允许可视化分子有效载荷的生物分布。但是，这些系统中的大多数没有报告从载体中释放药物，这对于设计优化的有效载荷输送系统至关重要，并且将对生物学效应有深入的了解。 寻求的项目将开发新型的聚合物纳米载体，可以显示将何时，何时以及多少分子有效载荷传递到特定的目标位点。以强烈的聚合物化学焦点为特色，将通过将一对氮氧化物氟夫妇掺入递送系统中来实现。当荧光团与氮氧化物紧密地保持时，荧光团进入了大量的状态，并观察到荧光的完全淬火。当从载体中释放载荷时，通过刺激诱导的共价连接的分离 - 将发生硝基氧化物和荧光团部分的分离，并立即观察到荧光的立即增加，从而允许定量递送。该分子的设计将使一个荧光团的开关与一个递送的分子的释放有关，从而导致可量化的释放量度。为了实现这种理想，已经确定了许多化学挑战，这些挑战是当前提案的核心，并将被解决，从而更深刻地了解了从聚合物纳米载体中传递的机制。该概念将在体外和体内研究中证明其实际适用性。

项目成果

Reporting pH-sensitive drug release via unpaired spin fluorescence silencing

通过不成对的自旋荧光沉默报告 pH 敏感的药物释放

• DOI: 10.1039/c7py01942d
• 发表时间: 2018
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: M. Eing;B. Olshausen;K. E. Fairfull-Smith;U. Schepers;C. Barner-Kowollik;J. P. Blinco
• 通讯作者: J. P. Blinco

Visible Light Activation of Spin-Silenced Fluorescence.

• DOI: 10.1002/chem.201800732
• 发表时间: 2018-08
• 期刊: Chemistry
• 作者: Matthias Eing;Bryan T. Tuten;J. Blinco;C. Barner‐Kowollik

Spin fluorescence silencing enables an efficient thermally driven self-reporting polymer release system

• DOI: 10.1039/c7py01437f
• 发表时间: 2017-10
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: H. Mutlu;Christian W. Schmitt;Nils Wedler-Jasinski;Hendrik Woehlk;K. Fairfull‐Smith;J. Blinco;C. Barne