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

Yi Han; Yanchao Liu; Xiaoyi Ma; Aijun Shen; Yiqiong Liu; Nopphon Weeranoppanant; Haiqing Dong; Yan Li; Tianbin Ren; Le Kuai; Bin Li; Maomao An; Yongyong Li

doi:10.1016/j.biomaterials.2021.120849

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

Biomaterials. 2021 Jul:274:120849. doi: 10.1016/j.biomaterials.2021.120849. Epub 2021 May 11.

Authors

Yi Han¹, Yanchao Liu², Xiaoyi Ma¹, Aijun Shen³, Yiqiong Liu¹, Nopphon Weeranoppanant⁴, Haiqing Dong¹, Yan Li¹, Tianbin Ren¹, Le Kuai⁵, Bin Li⁶, Maomao An⁷, Yongyong Li⁸

Affiliations

¹ Shanghai Tenth People's Hospital, Department of Medical Ultrasound, Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, PR China.
² Department of Clinical Pharmacy, Shanghai General Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200080, PR China.
³ Department of Medical Imaging, Tongji Hospital, Tongji University, Shanghai, 200065, PR China.
⁴ Department of Chemical Engineering, Burapha University, 169 Longhard Bangsaen, Saensook, Chonburi, 20131, Thailand.
⁵ Shanghai Dermatology Hospital, Tongji University School of Medicine, Shanghai, 200092, PR China.
⁶ Shanghai Dermatology Hospital, Tongji University School of Medicine, Shanghai, 200092, PR China. Electronic address: lib@shskin.com.
⁷ Shanghai Tenth People's Hospital, Department of Medical Ultrasound, Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, PR China. Electronic address: anmaomao@tongji.edu.cn.
⁸ Shanghai Tenth People's Hospital, Department of Medical Ultrasound, Department of Pharmacology, Tongji University School of Medicine, Shanghai, 200092, PR China. Electronic address: yongyong_li@tongji.edu.cn.

PMID: 34022739
DOI: 10.1016/j.biomaterials.2021.120849

Abstract

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 (~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.

Keywords: Albumin nanoparticles; Antibiotics delivery; Brain fungal infection; Chemotherapy-induced neutropenia; Neutrophil-targeting.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / therapeutic use
Antifungal Agents / therapeutic use
Antineoplastic Agents* / therapeutic use
Arm
Brain
Humans
Mice
Mycoses* / drug therapy
Neutropenia* / chemically induced
Neutropenia* / drug therapy
Neutrophils

Substances

Anti-Bacterial Agents
Antifungal Agents
Antineoplastic Agents