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Bioluminescent Bacterial Imaging In Vivo
Published on: November 4, 2012
Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise
1Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou 510515, China.
Abstract:
Traditional antibacterial procedures are getting inefficient due to the emergence of antimicrobial resistance, which makes alternative treatments in urgent demand. However, the selectivity toward infectious bacteria is still challenging. Herein, by taking advantage of the self-directed capture of infectious bacteria by macrophages, we developed a strategy to realize precise in vivo antibacterial photodynamic therapy (APDT) through adoptive photosensitizer-loaded macrophage transfer. TTD with strong reactive oxygen species (ROS) production and bright fluorescence was first synthesized and was subsequently formulated into TTD nanoparticles for lysosome targeting. TTD-loaded macrophages (TLMs) were constructed by direct incubation of TTD nanoparticles with macrophages, in which the TTD was localized in the lysosomes to meet the captured bacteria in the phagolysosomes. The TLMs could precisely capture and eradicate bacteria while being activated toward the proinflammatory and antibacterial M1 phenotype upon light illumination. More importantly, after subcutaneous injection, TLMs could effectively inhibit bacteria in the infected tissue through APDT, leading to good tissue recovery from severe bacterial infection. Overall, the engineered cell-based therapeutic approach shows great potential in the treatment of severe bacterial infectious diseases.
Insights
This study introduces a novel cell-based therapy using engineered macrophages loaded with a photosensitizer for precise antibacterial photodynamic therapy (APDT). This approach effectively targets and eliminates bacteria in vivo, offering a promising solution for antimicrobial resistance.
Area of Science:
- Biomedical Engineering
- Immunology
- Photodynamic Therapy
Background:
- Antimicrobial resistance necessitates novel antibacterial strategies.
- Targeting infectious bacteria selectively remains a significant challenge in current treatments.
Purpose of the Study:
- To develop a precise in vivo antibacterial photodynamic therapy (APDT) using photosensitizer-loaded macrophages.
- To leverage macrophage phagocytosis for targeted delivery and enhanced therapeutic outcomes.
Main Methods:
- Synthesized Tetraphenylethylene derivative (TTD) nanoparticles for reactive oxygen species (ROS) generation and fluorescence.
- Developed TTD-loaded macrophages (TLMs) for lysosome targeting and phagolysosome bacteria capture.
- Administered TLMs via subcutaneous injection and activated APDT with light illumination.
Main Results:
- TLMs precisely captured and eradicated bacteria upon light activation.
- TLMs exhibited M1 phenotype polarization, enhancing the proinflammatory and antibacterial response.
- In vivo APDT with TLMs effectively inhibited bacterial infection and promoted tissue recovery.
Conclusions:
- Engineered cell-based therapeutic approach shows significant potential for treating severe bacterial infections.
- Adoptive transfer of photosensitizer-loaded macrophages offers a precise and effective APDT strategy.

