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Adoptive macrophage directed photodynamic therapy of multidrug-resistant bacterial infection
Zehui Wang1, Anhua Wu2, Wen Cheng2
1State Key Laboratory of Fine Chemicals, Frontiers Science Center for Smart Materials Oriented Chemical Engineering, Dalian University of Technology, Dalian, 116024, China.
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.
Insights
This study introduces a novel therapy using macrophages loaded with a photosensitizer to combat multidrug-resistant (MDR) bacterial infections. The treatment achieved 100% survival in mice and rats, offering a promising solution for severe infections.
Area of Science:
- Immunology
- Photodynamic Therapy
- Infectious Diseases
Background:
- Multidrug-resistant (MDR) bacteria pose a significant threat, causing severe infections and high mortality, especially in immunocompromised patients.
- Current treatments for severe MDR bacterial infections are limited, necessitating the development of more effective strategies.
Purpose of the Study:
- To develop and evaluate an adoptive transfer therapy using macrophages loaded with a near-infrared photosensitizer (Lyso700D) to eliminate MDR bacteria.
- To enhance innate immunity and target bacteria within lysosomes for maximized photodynamic effect and minimized side effects.
Main Methods:
- Macrophages were loaded with Lyso700D and adoptively transferred to mice and rats infected with MDR bacteria.
- Photodynamic therapy was applied using near-infrared light irradiation.
- A specialized technique involving bone marrow-derived macrophages and implanted glass fiber was used for central nervous system infections in rats.
Main Results:
- The therapy efficiently eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) in mouse models.
- 100% survival was achieved in infected mice and rats, compared to 10% in control groups.
- Successful treatment of central nervous system bacterial infections in rats was demonstrated with 100% survival.
Conclusions:
- Adoptive transfer of photosensitizer-loaded macrophages is an effective and safe strategy for treating severe MDR bacterial infections.
- This approach offers a promising therapeutic avenue for future clinical applications in combating resistant bacterial pathogens.
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