Gmedhin Hatu, Schaefer Sebastian, Corrigan Nathaniel, Wu Peifeng, Gu Zi, Lenardon Megan D, Boyer Cyrille
Cluster for Advanced Macromolecular Design (CAMD) and Australian Centre for NanoMedicine (ACN), School of Chemical Engineering, UNSW, Sydney, NSW, 2052, Australia.
School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, NSW, 2052, Australia.
Macromol Biosci. 2025 Apr;25(4):e2400429. doi: 10.1002/mabi.202400429. Epub 2025 Jan 7.
Invasive fungal infections cause over 3.7 million deaths worldwide annually, underscoring the critical need for new antifungal agents. Developing selective antifungal agents is challenging due to the shared eukaryotic nature of both fungal and mammalian cells. Toward addressing this, synthetic polymers designed to mimic host defense peptides are promising new candidates for combating fungal infections. This study investigates well-defined multiblock terpolymers with specific arrangements of cationic, hydrophobic, and hydrophilic groups, as potential antifungal agents. The block sequence in these copolymers significantly impacts their minimum inhibition concentration (MIC) against Candida albicans and biocompatibility. Furthermore, compared to their statistical counterparts, these block polymers exhibit lower MIC values in certain instances. Notably, triblock terpolymers containing a central hydrophobic block present an enhanced antifungal efficacy and biocompatibility. These findings highlight the potential of block sequence-controlled polymers as a versatile platform for developing customized and targeted antifungal therapies.
侵袭性真菌感染每年在全球导致超过370万人死亡，这凸显了对新型抗真菌药物的迫切需求。由于真菌细胞和哺乳动物细胞都具有真核生物的共性，开发选择性抗真菌药物具有挑战性。为解决这一问题，设计用于模拟宿主防御肽的合成聚合物是对抗真菌感染的有前景的新候选物。本研究调查了具有特定阳离子、疏水和亲水基团排列的明确多嵌段三元共聚物作为潜在抗真菌剂的情况。这些共聚物中的嵌段序列对其针对白色念珠菌的最低抑菌浓度（MIC）和生物相容性有显著影响。此外，与统计型共聚物相比，这些嵌段聚合物在某些情况下表现出更低的MIC值。值得注意的是，含有中央疏水嵌段的三嵌段三元共聚物具有增强的抗真菌功效和生物相容性。这些发现突出了嵌段序列可控聚合物作为开发定制化和靶向抗真菌疗法的通用平台的潜力。
