Nanostar Sieving for multifunctional ADC Linkers: NanoLink

聚合物是由重复的化学单元组成的长分子，称为单体。聚乙二醇由乙二醇单单体组成，是一种广泛应用于生物医学的聚合物。聚乙二醇乙二醇酯被用来改善药物和蛋白质的水溶性，并调节它们在体内的转运和滞留。然而，目前组成聚乙二醇乙二醇酯的单体是不适应的；它们不能附着任何‘货物’，如药物、染料或细胞渗透剂。因此，聚乙二醇酯只能在聚合物链的起始和末端适配，而不能沿着聚合物主干适配，这限制了它们在生物医学应用中的应用。此外，目前制造工业规模聚合物的技术不允许轻松控制单体序列，因此即使使用不同的特殊-EG单体，将它们按特定顺序排列以制造定制聚合物将是具有挑战性的、耗时的和昂贵的。Exactmer是一家快速增长的SME，开发了一项突破性的新技术，用于制造具有准确长度和单体序列的聚合物：NanSTAR筛分。具有多个臂的中枢分子形成了巨大的“纳米星”。单体一个接一个地加入到手臂上，形成聚合物。每添加一次单体后，通过特殊设计的膜进行分子筛除杂物。重复这一过程，直到达到所需的单体序列，然后将长度和序列完全相同的聚合物从轮毂上切断并回收。NanoLink将使用NanSTAR筛分来制造钉子，包括Exactmer基于EG的全新单体序列，每个包含一个侧基，旨在连接有用的货物。聚合后，这些单体将形成被称为PEGabets的多功能钉子，并将被用作抗体-药物-结合物(ADC)的连接物。ADC已被开发为癌症治疗的“神奇子弹”，直接将有毒有效载荷传递给癌细胞；绕过健康细胞。通过增加水溶性、药物与抗体的比例以及能够加入多功能成分，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.