The increasing prevalence of invasive fungal infections and drug resistance highlights the urgent need for alternative antifungal strategies. This study synthesized a guanosine-functionalized polypeptide (PArg20) with a bacteriophage-like action process, which demonstrated excellent antifungal activity and good biocompatibility. PArg20 mimics the three-step infection process of a bacteriophage, exhibiting a "adsorption-penetration-destroy" action process similar to that of a bacteriophage. Initially, electrostatic interactions promote the adsorption of the membrane for targeting, followed by membrane penetration driven by translocation ability and local membrane perturbation. Once internalized, PArg20 triggers a series of programmed intracellular destruction, including mitochondrial dysfunction, oxidative stress, and nuclear rupture. Compared with clinically used antifungal drugs, PArg20 reduces the time required to eliminate fungal infections from over 2 hours to only 10 minutes, and shows no significant tendency towards drug resistance after 15 consecutive passages. In mouse corneal and systemic fungal infection models, PArg20 significantly reduces fungal burden and inflammation. Overall, the bacteriophage-like action process exhibited by PArg20 provides an antifungal method that may help combat fungal infections while limiting the emergence of drug resistance. This research was published in ACS Nano under the title "Membrane-Targeting Poly(Amino Acids) with a Phage-Like Action Process for Antifungal Therapy".
References: DOI: 10.1021/acsnano.5c13661