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Macrophage membrane-camouflaged dual drug-based biomimetic pH-responsive nanomedicine for synergistic antifungal-antioxidant therapy in oral candidiasis.

Kaiwen Bao,Yunfan Li,Yantao Li,Shuai Wu,Sheng Ni,Xiong Zhao,Ya Wang,Yi Liang,Qiao Chen,Xinmei Duan,Da Sun,Li Zhu,Wei Wu

Published 2025 in Acta Biomaterialia

ABSTRACT

The escalating challenges of antifungal drug resistance, toxicity, and limited therapeutic strategies for oral candidiasis (OC) necessitate innovative treatment approaches. This study developed a pH-responsive baicalein-based nanocarrier by coupling baicalein with phenylboronic acid-functionalized polymethyl vinyl ether-maleic anhydride to encapsulate amphotericin B (AMB). The nanocarrier was further camouflaged with macrophage membranes, forming a biomimetic dual-drug nanoplatform (MPPB@A NPs) for synergistic antifungal-antioxidant therapy against OC. MPPB@A NPs leverage macrophage membrane coating to enhance active targeting of β-glucans on C. albicans, while borate ester bonds enable pH-responsive drug release at pH 5.5. MPPB@A NPs were demonstrated to effectively disrupt C. albicans biofilms and scavenge reactive oxygen species (ROS). In murine OC models, MPPB@A NPs significantly reduced oral fungal burden (11.17% of the free AMB group) and alleviated oxidative stress. Subsequently, ROS-mediated inflammation was reduced. Furthermore, MPPB@A NPs exhibited the favorable biocompatibility, including hemolysis rates below 5%, reduced cytotoxicity, and significantly lower nephrotoxicity compared to free AMB. Therefore, this study provides a promising strategy to overcome AMB toxicity and resistance while promoting the synergistic antifungal-antioxidant therapy for OC management. STATEMENT OF SIGNIFICANCE: Current oral candidiasis therapies face challenges of drug resistance and systemic toxicity. This study has the potential to address these limitations using a biomimetic nanoplatform combining macrophage membrane camouflage with a pH-responsive carrier, enabling targeted dual-drug delivery to infection sites. The membrane coating facilitates tissue accumulation, while pH-triggered release delivers amphotericin B within acidic fungal biofilms, disrupting Candida albicans. Baicalein, as a nanocarrier component, exhibits antioxidant and anti-inflammatory effects. This strategy synergistically combats fungal infection and associated oxidative stress damage while significantly enhancing drug biocompatibility and reducing systemic toxicity, offering a clinically translatable solution.

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