Nanostar Sieving for multifunctional ADC Linkers: NanoLink

聚乙二醇（PEG）是由乙二醇（EG）单体组成的一种聚合物，广泛应用于生物医学领域。PEG用于改善药物和蛋白质的水溶性，并调节其在体内的转运和保留。然而，目前构成PEG的EG单体不具有适应性;它们不能附着任何“货物”，如药物，染料或细胞渗透剂。因此，PEG只能在聚合物链的开始和末端进行调整，而不能沿着聚合物主链，限制了它们在生物医学应用中的应用。此外，目前工业规模的聚合物制造技术不允许对单体序列进行简单控制，因此即使使用不同的特殊EG单体，将它们以特定顺序排列以制造定制聚合物也具有挑战性，耗时且昂贵。Exactmer是一家快速发展的SME，开发了一种突破性的新技术，用于制造具有精确长度和单体序列的聚合物：纳米星筛选。具有多个臂的枢纽分子形成大的“纳米星”。单体被一个接一个地添加到臂上以形成聚合物。在每次单体添加后，通过分子筛通过专门设计的膜除去碎片。重复该过程，直到达到所需的单体序列，然后从枢纽上切下精确长度和序列的聚合物并回收。NanoLink将使用Nanostar Sieving来制备PEG，其中包含Exactmer的全新序列，基于EG的单体，每个单体都包含一个旨在连接有用货物的侧基。当聚合时，这些单体将形成被称为“PEGabet”的多功能PEG，并且将用作抗体-药物-缀合物（ADC）的接头ADC已被开发为用于癌症治疗的“魔术子弹”，将毒性有效载荷直接递送至癌细胞;绕过健康细胞。通过增加水溶性，药物与抗体的比例，并使多功能成分的掺入，PEGabets可以彻底改变ADC疗法。

Polymers are long molecules, comprising repeated chemical units known as monomers.Polyethylene glycol (PEG), comprising ethylene glycol (EG) monomers, is a polymer widely used in biomedicine. PEG is used to improve the water-solubility of drugs and proteins, and to regulate their transport and retention in the body.However, the current EG monomers that make up PEGs are unadaptable; they cannot attach any 'cargo', such as drugs, dyes, or cell-penetrating agents. Consequently, PEGs can only be adapted at the beginning and end of the polymer chains, and not along the polymer backbone, limiting what they can achieve in biomedical applications. Furthermore, current techniques that make polymers on industrial scales do not allow easy control over the monomer sequences, and so even if different, specialised-EG monomers were used, arranging them in a specific order to make bespoke polymers would be challenging, time-consuming and expensive.Exactmer is a fast-growing SME, developing a breakthrough new technology for the fabrication of polymers with exact lengths and monomer sequences: Nanostar Sieving. Hub molecules with multiple arms forms large 'nanostars'. Monomers are added to the arms, one-by-one, to form polymers. After each monomer addition, debris is removed by molecular sieving through specially designed membranes. The process is repeated until the desired sequence of monomers is reached, and then the exact-length-and-sequence polymers are cut off the hubs and recovered.NanoLink will use Nanostar Sieving to make PEGs, comprising sequences of Exactmer's completely-new, EG-based monomers, each containing a side-group designed to attach useful cargo. When polymerised, these monomers will form multi-functional PEGs known as 'PEGabets', and will be used as linkers for Antibody-Drug-Conjugates (ADCs).ADCs have been developed as a 'magic-bullet' for cancer treatment, delivering toxic payloads directly to cancer cells; bypassing healthy cells. By increasing water-solubility, drug-to-antibody ratios and enabling incorporation of multifunctional components, PEGabets could revolutionise ADC therapeutics.