Synthetic macromolecules as therapeutics that overcome resistance in cancer and microbial infection

Synthetic macromolecular antimicrobials have shown efficacy in the treatment of multidrug resistant (MDR) pathogens. These synthetic macromolecules, inspired by Nature's antimicrobial peptides (AMPs), mitigate resistance by disrupting microbial cell membrane or targeting multiple intracellular proteins or genes. Unlike AMPs, these polymers are less prone to degradation by proteases and are easier to synthesize on a large scale. Recently, various studies have revealed that cancer cell membrane, like that of microbes, is negatively charged, and AMPs can be used as anticancer agents. Nevertheless, efforts in developing polymers as anticancer agents has remained limited. This review highlights the recent advancement in the development of synthetic biodegradable antimicrobial polymers (e.g. polycarbonates, polyesters and polypeptides) and anticancer macromolecules including peptides and polymers. Additionally, strategies to improve their in vivo bioavailability and selectivity towards bacteria and cancer cells are examined. Lastly, future perspectives, including use of artificial intelligence or machine learning, in the development of antimicrobial and anticancer macromolecules are discussed.