Tan Jason, Tay Joyce, Hedrick James, Yang Yi Yan
Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore, 138669, Singapore; Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore, 637371, Singapore.
IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, United States.
Biomaterials. 2020 Sep;252:120078. doi: 10.1016/j.biomaterials.2020.120078. Epub 2020 May 5.
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.
合成高分子抗菌剂已在治疗多重耐药（MDR）病原体方面显示出疗效。这些受天然抗菌肽（AMP）启发的合成大分子，通过破坏微生物细胞膜或靶向多种细胞内蛋白质或基因来减轻耐药性。与AMP不同，这些聚合物不太容易被蛋白酶降解，并且更容易大规模合成。最近，各种研究表明，癌细胞膜与微生物细胞膜一样带负电荷，并且AMP可作为抗癌剂使用。然而，开发聚合物作为抗癌剂的努力仍然有限。本综述重点介绍了合成可生物降解抗菌聚合物（如聚碳酸酯、聚酯和多肽）以及包括肽和聚合物在内的抗癌大分子的最新进展。此外，还研究了提高其体内生物利用度以及对细菌和癌细胞选择性的策略。最后，讨论了抗菌和抗癌大分子开发中的未来前景，包括人工智能或机器学习的应用。
