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Published on: October 28, 2015
A Strategy of On-Demand Immune Activation for Antifungal Treatment Using Near-Infrared Responsive Conjugated Polymer
Zijuan Wang1, Shuyi Qu2, Dong Gao3
1School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300130, China.
Abstract:
Pathogenic fungal infection is a major clinical threat because pathogenic fungi have developed resistant mechanisms to evade the innate immune response, especially interactions with macrophages. Herein, a strategy to activate immune responses of macrophages to fungi based on near-infrared (NIR) responsive conjugated polymer nanoparticles (CPNs-M) is reported for antifungal immunotherapy. Under NIR light irradiation, CPNs-M exposes β-glucan on the surface of fungal conidia by photothermal damage and drug released from CPNs-M. The exposed β-glucan elicits macrophage recognition and subsequently activates calcium-calmodulin (Ca2+-CaM) signaling followed by the LC3-associated phagocytosis (LAP) pathway to kill fungal conidia. Consequently, a remarkable elimination of intracellular fugal conidia and successful treatment of fungal pneumonia are achieved. This remote regulation strategy to restore pathogen-immune cell interaction on demand provides a new insight into combatting intractable intracellular infections.
Insights
This study introduces near-infrared (NIR) responsive nanoparticles to treat fungal infections. These nanoparticles activate macrophages to clear fungi, offering a new approach to antifungal immunotherapy.
Area of Science:
- Immunology
- Nanotechnology
- Infectious Diseases
Background:
- Pathogenic fungi pose a significant clinical challenge due to resistance to innate immune responses, particularly macrophage interactions.
- Developing effective strategies against intracellular fungal infections remains crucial.
Purpose of the Study:
- To develop a novel antifungal immunotherapy using near-infrared (NIR) responsive conjugated polymer nanoparticles (CPNs-M).
- To investigate the mechanism of CPNs-M in activating macrophage-mediated fungal clearance.
Main Methods:
- CPNs-M were designed to be responsive to NIR light for targeted drug release and fungal surface modification.
- The study examined the exposure of fungal β-glucan, macrophage recognition, calcium-calmodulin (Ca2+-CaM) signaling, and LC3-associated phagocytosis (LAP) pathway activation.
Main Results:
- NIR irradiation of CPNs-M led to photothermal damage of fungal conidia, exposing β-glucan.
- Exposed β-glucan triggered macrophage recognition and subsequent activation of the Ca2+-CaM and LAP pathways.
- Significant elimination of intracellular fungal conidia and successful treatment of fungal pneumonia were observed.
Conclusions:
- CPNs-M provides a remote-controlled strategy to restore pathogen-immune cell interactions for enhanced antifungal immunity.
- This approach offers a promising new avenue for combating intractable intracellular fungal infections.
