Antibiotics armed neutrophils as a potential therapy for brain fungal infection caused by chemotherapy-induced neutropenia

Chemotherapy-induced neutropenia, a symptom of neutrophil depletion, makes cancer patients highly susceptible to invasive fungal infection with substantial morbidity and mortality. To address the cryptococcal brain infection in this condition, this study attempts to arm neutrophils (NEs) with antibiotics to potentiate the antifungal capability of NEs. To allow effective integration, amphotericin B, a potent antibiotic, is assembled with albumin nanoparticles through hydrophobic and hydrogen-bond interactions to form AmB@BSA nanoparticles (A-NPs). The nutrient composition (albumin) and virus-like size (similar to 40 nm) facilitate efficient uptake of A-NPs by NEs to construct the antibiotics-armed NEs. It is demonstrated that the armed NEs can maintain the intrinsic biological functions of NEs, such as cell viability and capacity of migration to an inflammatory site. In a neutropenic mouse model of brain fungal infection, the treatment with the armed NEs allows for preventing fungal invasion more effectively than that with the native NEs, without the apparent systemic toxicity. Such a synergistic anti-infection system maximizes the antifungal effects by taking advantage of NEs and antibiotics. It provides a potential NEs-mediated therapeutic approach for treating fungal infection caused by chemotherapy-induced neutropenia.