Antifungal Encapsulated into Ligand-Functionalized Nanoparticles with High Specificity for Macrophages

Area of Science:

• Nanomedicine
• Infectious Diseases
• Immunology

Background:

• Infectious diseases caused by intracellular microorganisms like Histoplasma capsulatum pose global health challenges.
• Drug encapsulation in nanoparticles (NPs) improves drug delivery, bioavailability, and targeted action.

Purpose of the Study:

• To develop and evaluate anti-F4/80 antibody-functionalized polymeric nanoparticles (NPs) for targeted delivery of Itraconazole (ITZ) to macrophages.
• To assess the efficacy of ITZ-loaded NPs against H. capsulatum in vitro and their impact on macrophage inflammatory responses.

Main Methods:

• Core-shell polymeric NPs were synthesized encapsulating Itraconazole (ITZ).
• NPs were functionalized with anti-F4/80 antibodies for macrophage targeting.
• In vitro assays evaluated NP uptake, antifungal activity against H. capsulatum, and cytotoxicity in macrophages.
• Gene expression of inflammatory cytokines (IL-1, INF-Y, IL-6, IL-10) was analyzed.

Main Results:

• Functionalized NPs showed significantly higher uptake by macrophages compared to bare NPs.
• Anti-F4/80 antibody-functionalized NPs loaded with 0.007 µg/mL ITZ effectively eliminated H. capsulatum without macrophage cytotoxicity.
• Encapsulated ITZ modulated the expression of anti-inflammatory and pro-inflammatory cytokines.
• Antibody functionalization enhanced the natural antifungal response and exerted a synergistic effect, inhibiting intracellular fungal growth.

Conclusions:

• Anti-F4/80 antibody-functionalized NPs offer a promising strategy for targeted macrophage therapy against intracellular pathogens like H. capsulatum.
• This approach enhances NP endocytosis and intracellular drug concentration, leading to improved therapeutic outcomes.
• The synergistic effect of targeted drug delivery and enhanced host response presents a novel avenue for infectious disease treatment.