International journal of nanomedicine · 2026
PVP-Stabilized Ag@SiO2 Nanocarriers for Usnic Acid: Physicochemical Characterization and Exploratory in vitro Anticancer, Antimicrobial, and Immunomodulatory Activity.
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Pyrczak-Felczykowska Agnieszka, Kowalska Agata, Adamska Elżbieta, Bogucka Aleksandra, Zima Katarzyna, Nowicki Dariusz, Żuczek Klaudia, Wcisło Anna, Grobelna Beata, Urbanowicz Krzysztof, Zabielska-Kaczorowska Magdalena, Herman-Antosiewicz Anna
Аннотация
BACKGROUND: Usnic acid (UA) is a lichen-derived metabolite with recognized anticancer, anti-inflammatory, and antibacterial properties; however, its clinical application is limited by poor aqueous solubility and dose-dependent toxicity. This study aimed to develop a multifunctional nanosystem to improve UA aqueous dispersibility and efficacy against breast cancer cells in vitro.
METHODS: A nanosystem consisting of a silver core-silica shell coated with polyvinylpyrrolidone (PVP) and conjugated UA (Ag@SiO2/PVP/UA) was synthesized and characterized regarding morphology, physicochemical properties, colloidal stability, drug loading, and release behavior. Antiproliferative activity was evaluated using breast cancer cells (MCF-7 and MDA-MB-231). Cytotoxicity was assessed using the MTT viability assay, reactive oxygen species (ROS) production by flow cytometry, and metabolic alterations through LC-MS/MS-based metabolomic analysis. Antimicrobial activity against Gram-positive and Gram-negative bacteria was expressed by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Immunomodulatory properties were assessed in human peripheral blood mononuclear cells (PBMCs) using ELISA, while fibroblast migration was analyzed using an in vitro wound healing assay.
RESULTS: The developed nanostructures exhibited a stable core-shell architecture, uniform particle size (~200 nm), and enhanced hydrophilicity, resulting in improved aqueous dispersibility and sustained UA release. Nanoencapsulation significantly enhanced UA's anticancer activity against breast cancer cells in vitro while maintaining lower toxicity toward normal cells. Mechanistically, Ag@SiO2/PVP/UA induced ROS-mediated oxidative stress and metabolic reprogramming associated with altered purine metabolism, lipid biosynthesis, redox balance, and activation of glycolytic pathways. The nanosystem also demonstrated broad-spectrum antimicrobial activity, including improved efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and selected Gram-negative bacteria, while exerting immunomodulatory effects by reducing pro-inflammatory cytokine secretion and enhancing IL-10 production without affecting fibroblast migration.
CONCLUSION: Ag@SiO2/PVP/UA represents a promising multifunctional therapeutic platform combining enhanced anticancer efficacy with antimicrobial and anti-inflammatory properties, potentially improving the therapeutic applicability of UA.
METHODS: A nanosystem consisting of a silver core-silica shell coated with polyvinylpyrrolidone (PVP) and conjugated UA (Ag@SiO2/PVP/UA) was synthesized and characterized regarding morphology, physicochemical properties, colloidal stability, drug loading, and release behavior. Antiproliferative activity was evaluated using breast cancer cells (MCF-7 and MDA-MB-231). Cytotoxicity was assessed using the MTT viability assay, reactive oxygen species (ROS) production by flow cytometry, and metabolic alterations through LC-MS/MS-based metabolomic analysis. Antimicrobial activity against Gram-positive and Gram-negative bacteria was expressed by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Immunomodulatory properties were assessed in human peripheral blood mononuclear cells (PBMCs) using ELISA, while fibroblast migration was analyzed using an in vitro wound healing assay.
RESULTS: The developed nanostructures exhibited a stable core-shell architecture, uniform particle size (~200 nm), and enhanced hydrophilicity, resulting in improved aqueous dispersibility and sustained UA release. Nanoencapsulation significantly enhanced UA's anticancer activity against breast cancer cells in vitro while maintaining lower toxicity toward normal cells. Mechanistically, Ag@SiO2/PVP/UA induced ROS-mediated oxidative stress and metabolic reprogramming associated with altered purine metabolism, lipid biosynthesis, redox balance, and activation of glycolytic pathways. The nanosystem also demonstrated broad-spectrum antimicrobial activity, including improved efficacy against methicillin-resistant Staphylococcus aureus (MRSA) and selected Gram-negative bacteria, while exerting immunomodulatory effects by reducing pro-inflammatory cytokine secretion and enhancing IL-10 production without affecting fibroblast migration.
CONCLUSION: Ag@SiO2/PVP/UA represents a promising multifunctional therapeutic platform combining enhanced anticancer efficacy with antimicrobial and anti-inflammatory properties, potentially improving the therapeutic applicability of UA.