Dendritic Antifungal Peptides as Potent Agents against Drug-Resistant <i>Candida albicans</i> and Biofilm

<i>Candida albicans</i> infection is a major public health problem, exacerbated by the emergence of drug-resistant fungi with the widespread use of antifungal drugs. Therefore, the development of novel antifungal drugs for drug-resistant <i>C. albicans</i> infections is crucial. We constructed a series of dendritic antifungal peptides (AFPs) with different chain lengths of fatty acids as hydrophobic ends and 2 or 3 protease-stable repeats (Arg-Pro) as dendritic peptide branches. Among them, C₄-3RP exhibited excellent antidrug-resistant fungal and biofilm activity (GM_all = 5.04 μM) and was nontoxic. Furthermore, C₄-3RP demonstrated high protease stability and salt ion tolerance, making it highly effective in murine skin infection mediated by <i>C. albicans</i><i>.</i> In addition, C₄-3RP uses multiple mechanisms of action to achieve excellent antifungal effects. In conclusion, the construction of dendritic peptides holds substantial potential in the treatment of fungal infections and provides a broader perspective on the design of peptide-based antifungal drugs.