A Strategy of On-Demand Immune Activation for Antifungal Treatment Using Near-Infrared Responsive Conjugated Polymer Nanoparticles.

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.