Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection

Zehui Wang, Anhua Wu, Wen Cheng, Yuhe Li, Dingxuan Li, Lai Wang, Xinfu Zhang () and Yi Xiao
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Zehui Wang: Dalian University of Technology
Anhua Wu: Shengjing Hospital of China Medical University
Wen Cheng: Shengjing Hospital of China Medical University
Yuhe Li: Shengjing Hospital of China Medical University
Dingxuan Li: Dalian University of Technology
Lai Wang: Dalian University of Technology
Xinfu Zhang: Dalian University of Technology
Yi Xiao: Dalian University of Technology

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer (Lyso700D) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection.

Date: 2023
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DOI: 10.1038/s41467-023-43074-9

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