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.

当前提案的总体目标是开发一种技术平台，可以通过结合可切换的荧光片段来跟踪和量化分子释放机制（例如药物释放），该荧光片段能够同时可视化和量化有效载荷的传递。聚合物纳米颗粒作为药物递送载体的发展促进了多种治疗方法的有效靶向释放策略。当与显像剂结合使用时，这些纳米颗粒可以使分子有效载荷的生物分布可视化。然而，这些系统中的大多数没有报告药物从载体的释放，这是一个重要的方面，这对于优化有效载荷传递系统的设计至关重要，并将使深入了解生物效应成为可能。该项目将开发新型聚合物纳米载体，它可以显示在何处、何时以及有多少分子负载被递送到特定的目标位点。具有强大的聚合物化学焦点，这将通过将氮氧化物-荧光基团偶联纳入输送系统来实现。当一个荧光团靠近氮氧化物时，荧光团进入前荧光状态，并观察到荧光完全猝灭。当负载通过刺激诱导的共价键断裂从载体中释放出来时，氮氧化物和荧光团部分将发生分离，并立即观察到荧光的增加，从而允许定量递送。这些分子将被设计成这样，一个荧光团的开关将与一个传递分子的释放相关，从而导致释放的可量化测量。为了实现这一理想，已经确定了许多化学挑战，这些挑战是当前提案的核心，并将得到解决，从而对聚合物纳米载体的递送机制有更深刻的理解。该概念将在体外和体内研究中得到证明，以证明其实际适用性。

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