RESUMEN
Natural antimicrobial peptides (AMPs) and enzymes (AMEs) are promising non-antibiotic candidates against antimicrobial resistance but suffer from low efficiency and poor stability. Here, we develop peptide nanozymes which mimic the mode of action of AMPs and AMEs through de novo design and peptide assembly. Through modelling a minimal building block of IHIHICI is proposed by combining critical amino acids in AMPs and AMEs and hydrophobic isoleucine to conduct assembly. Experimental validations reveal that IHIHICI assemble into helical ß-sheet nanotubes with acetate modulation and perform phospholipase C-like and peroxidase-like activities with Ni coordination, demonstrating high thermostability and resistance to enzymatic degradation. The assembled nanotubes demonstrate cascade antifungal actions including outer mannan docking, wall disruption, lipid peroxidation and subsequent ferroptotic death, synergistically killing >90% Candida albicans within 10 min on disinfection pad. These findings demonstrate an effective de novo design strategy for developing materials with multi-antimicrobial mode of actions.
Asunto(s)
Antifúngicos , Candida albicans , Antifúngicos/farmacología , Antifúngicos/química , Candida albicans/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Nanotubos/química , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/química , Peroxidación de Lípido/efectos de los fármacos , Péptidos/farmacología , Péptidos/químicaRESUMEN
Esophageal squamous cell carcinoma (ESCC) remains a major health challenge, with cisplatin (CDDP) being the primary chemotherapy drug, albeit accompanied by resistance development over time. This study introduces a novel platinum drug delivery system, EMLipoPt(IV), tailored to enhance platinum uptake and diminish its inactivation, providing a solution to CDDP resistance in ESCC. By synthesizing a fusion of the ESCC cell membrane with liposomal Pt(IV) prodrugs, we integrated the tumor-targeting capacity of the ESCC membrane with the inactivation resistance of Pt(IV) prodrugs. In vivo and in vitro evaluations illustrated EMLipoPt(IV)'s robustness against inactivating agents, superior tumor-targeting capacity, and remarkable ability to suppress CDDP-resistant tumor progression. Importantly, the biosafety profile of EMLipoPt(IV) surpassed existing treatments, offering a prolonged survival rate in animal models. Collectively, this work not only presents a pioneering approach in ESCC chemotherapy but also provides a blueprint for combating drug resistance in other cancers, emphasizing the broader potential for tailored drug delivery systems.