Nanostar Sieving for multifunctional ADC Linkers: NanoLink

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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.