Nanostar Sieving for multifunctional ADC Linkers: NanoLink

用于多功能 ADC 连接器的 Nanostar 筛分：NanoLink

• 批准号: 10043819
• 金额: $ 44.33万
• 依托单位: EXACTMER LIMITED
• 依托单位国家: 英国
• 项目类别: Collaborative R&D
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=10043819
• 关键词: Nanostar; Sieving; multifunctional; ADC; Linkers

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.

聚合物是长分子，由称为单体的重复化学单位组成。聚乙二醇（PEG）是一种广泛应用于生物医学的聚合物，由乙二醇（EG）单体组成。聚乙二醇用于改善药物和蛋白质的水溶性，并调节其在体内的运输和保留。然而，目前组成peg的EG单体是不适应的；它们不能附着任何“货物”，如药物、染料或细胞穿透剂。因此，peg只能在聚合物链的开始和结束处适应，而不能沿着聚合物主链适应，限制了它们在生物医学应用中的应用。此外，目前在工业规模上制造聚合物的技术不允许简单地控制单体序列，因此，即使使用不同的、专门的eg单体，按照特定的顺序排列它们来制造定制的聚合物将是具有挑战性的，耗时且昂贵的。Exactmer是一家快速发展的中小企业，开发了一项突破性的新技术，用于制造具有精确长度和单体序列的聚合物：Nanostar筛分。具有多个臂的轮毂分子形成了巨大的“纳米星”。单体一个接一个地加到臂上，形成聚合物。每次添加单体后，通过特殊设计的膜进行分子筛分，去除碎屑。该过程重复进行，直到达到所需的单体序列，然后将长度和序列相同的聚合物从轮毂上切断并回收。NanoLink将使用Nanostar筛分技术制造peg，由Exactmer全新的以eg为基础的单体组成，每个单体都包含一个侧基，用于附着有用的货物。当聚合时，这些单体将形成被称为“pegabet”的多功能peg，并将用作抗体-药物偶联物（adc）的连接物。adc已被开发为癌症治疗的“神奇子弹”，直接向癌细胞提供有毒有效载荷；绕过健康细胞通过提高水溶性，药物-抗体比和使多功能成分的结合，PEGabets可以彻底改变ADC治疗方法。