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

模仿自然一直是科学的驱动力。随着研究下降到分子水平，模拟细胞和细胞区室成为焦点，并被确立为合成生物学。由于形成用于特定任务的单独隔室对于活细胞的形成至关重要，因此从头开始重建这些隔室具有很高的科学兴趣。为了这样做，形成完全合成的隔室，两亲性嵌段共聚物已被证明是一种可行的方式来生产人工囊泡，这被称为聚合物囊泡。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，以便在长期内也排除毒副作用。在该项目中，将使用多肽样聚合物，即所谓的类多肽。这些大分子在化学上与它们的生物学对应物非常相似，并且由生物学上可裂解的酰胺键组成。这些聚合物的另一个优点是它们的简单合成。根据文献，可以在3个步骤内容易地获得具有不同官能度的各种单体。此外，一旦单体可用，聚合物本身也容易获得。因此，类多肽是用于产生完全生物相容的聚合物囊泡的合适选择。一旦单体可用，就需要合成不同的聚合物，以确定哪些聚合物形成所需的结构，并可用于进一步研究。这必须对用于2个单独应用的聚合物进行，即药物递送系统（DDS）和纳米反应器。如果设计用于DDS，聚合物囊泡应该在到达最终目的地后分解，但在到达之前保持完整。货物首先被安全地装载在聚合物囊泡中，然后在其目的地被有效地释放。然而，为了仅到达特定的目的地，聚合物囊泡需要配备有官能化的表面，以使它们仅被识别为某些细胞类型。由于类多肽的化学结构，此类改性引发剂易于获得。除此之外，染料的表面官能化对于为DDS以及纳米反应器设计的聚合物囊泡的成像原因是重要的。后者需要在所有条件下都是稳定的，并且在任何时候都不应该将其封闭的催化剂（例如酶）释放到外部基质中。相比之下，聚合物囊泡膜现在是门控和控制催化剂的活性。因此，该项目的目标是从灵活的类多肽系统中创建聚合物囊泡，该系统可以分别针对不同的应用（DDS和纳米反应器）进行微调。

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.