Fine-Tuning Biodegradable Polymersome Membrane Permeability by the use of a Fine-tuned Polypeptoid Composition

通过使用微调的多肽组合物微调可生物降解的聚合物膜的渗透性

• 批准号: 248710858
• 负责人: Dr. Jens Gaitzsch
• 金额: --
• 依托单位: Leibniz-Institut für Polymerforschung Dresden (IPF)
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/248710858?language=en
• 关键词: Fine; Tuning; Biodegradable; Polymersome; Membrane

Mimicking nature has always been a driving force in science. With research coming down to the molecular level, mimicking cells and cellular compartments came into focus and was established as synthetic biology. Since the formation of separate compartments for specific tasks is essential in the formation of living cells, rebuilding such compartments from the scratch is of high scientific interest. In order to do so form totally synthetic compartments, amphiphilic block copolymers have proven to be a feasible way to produce artificial vesicles, which are called polymersomes. Until now, the polymers used are mainly non-biodegradable. When it comes to a biological application, however, these polymers should be totally biodegradable in order to rule out toxic side-effects also in the long term. In this project, polypeptide-like polymers, the so-called polypeptoids are to be used. These macromolecules are chemically very similar to their biological counterpart and are built up of biologically cleavable amide bonds. Another advantage of these polymers is their simple synthesis. According to literature a variety of monomers with different functionalities can be accessed easily within 3 steps. In addition, the polymer itself is also readily accessible once the monomers are available. Hence, polypeptoids are a suitable choice for creating polymersomes which are fully biologically compatible. Once the monomers are available, different polymers need to be synthesized to see, which ones form the desired structures and are feasible for further studies. This has to be done for polymers for 2 separate applications, the drug-delivery-system (DDS) and the nanoreactors. If designed for DDS, the polymersomes ought to disintegrate once they reach their final destination, but stay intact beforehand. The cargo is the securely stowed in the polymersomes at first at efficiently released at its destination. However, in order to reach a specific destination only, the polymersomes need to be equipped with a functionalized surface for them to be recognized be certain cell types only . Due to the chemical structure of the polypeptoids, such modified initiators are readily accessible. Apart from that, surface functionalization with dyes is important for imaging reasons for polymersomes designed for DDS as well as nanoreactors. The latter ones though need to be stable at all conditions and should not release their enclosed catalyst (e.g. an enzyme) into the outside matrix at any time. In contrast, the polymersome membrane is now to gate and control the activity of the catalyst. Hence, it is the goal of this project to create polymersomes out of a flexible polypeptoid system, which can be fine-tuned specifically for different applications, DDS as well as nanoreactors, separately.

模仿自然一直是科学的推动力。随着研究下降到分子水平，模拟细胞和细胞室成为焦点，并被建立为合成生物学。由于在活细胞的形成过程中，为特定任务形成独立的区室是必不可少的，因此从头开始重建这样的区室具有很高的科学兴趣。为了形成完全合成的隔室，两亲嵌段共聚物已被证明是产生人工囊泡的可行方法，这些囊泡被称为聚合体。到目前为止，使用的聚合物主要是不可生物降解的。然而，当涉及到生物应用时，这些聚合物应该是完全可生物降解的，以排除长期的毒副作用。在这个项目中，将使用多肽样聚合物，即所谓的多肽。这些大分子在化学上与它们的生物对应物非常相似，并且是由生物上可切割的酰胺键构成的。这些聚合物的另一个优点是它们的合成简单。根据文献，在3步内可以轻松地获得具有不同功能的各种单体。此外，一旦单体可用，聚合物本身也很容易获得。因此，多肽是创造具有完全生物相容性的聚合体的合适选择。一旦单体可用，就需要合成不同的聚合物，看看哪一种形成所需的结构，并为进一步的研究提供可行性。对于两种不同应用的聚合物，即药物输送系统（DDS）和纳米反应器，必须这样做。如果是为DDS设计的，聚合体应该在到达最终目的地后分解，但在到达目的地之前保持完整。货物首先安全地装载在聚合体中，然后在目的地有效地释放。然而，为了只到达特定的目的地，聚合体需要配备一个功能化的表面，使它们只能被识别为特定的细胞类型。由于多肽的化学结构，这种改性引发剂很容易获得。除此之外，染料的表面功能化对于为DDS和纳米反应器设计的聚合体的成像原因很重要。后者需要在任何条件下都保持稳定，并且不应该在任何时候将其封闭的催化剂（例如酶）释放到外部基质中。相比之下，聚合体膜现在是门和控制催化剂的活性。因此，这个项目的目标是从一个灵活的多肽系统中创造聚合体，它可以针对不同的应用进行微调，分别用于DDS和纳米反应器。

项目成果

Nanoscale detection of metal-labeled copolymers in patchy polymersomes

• DOI: 10.1039/c4py01508h
• 发表时间: 2015-03
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: Lorena Ruiz-Pérez;J. Madsen;Efrosyni Themistou;J. Gaitzsch;Le Messager;S. Armes;G. Battaglia