Lysosome-Targeting Aggregation-Induced Emission Nanoparticle Enables Adoptive Macrophage Transfer-Based Precise Therapy of Bacterial Infections.
Peng WangBiru WuMin LiYuchen SongChengjian ChenGuangxue FengDuo MaoFang HuJie LiuPublished in: ACS nano (2023)
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.
Keyphrases
- photodynamic therapy
- cell therapy
- antimicrobial resistance
- reactive oxygen species
- cancer therapy
- infectious diseases
- drug delivery
- wound healing
- silver nanoparticles
- single cell
- stem cells
- fluorescent probe
- wastewater treatment
- anti inflammatory
- ultrasound guided
- living cells
- climate change
- single molecule
- risk assessment