Development of a Self-Luminescent Living Bioreactor for Enhancing Photodynamic Therapy in Breast Cancer.
Yanian XiongYingtung LoHuizhu SongJianzhong LuPublished in: Bioconjugate chemistry (2024)
The penetration ability of visible light (<2 mm) and near-infrared (NIR) light (∼1 cm) remarkably impairs the therapeutic efficacy and clinical applications of photodynamic therapy (PDT). To address the limitation of light penetration depth, a novel self-luminescent bacterium, teLuc.FP-EcN, has been engineered through transfection of a fusion expression plasmid containing the luciferase gene teLuc and bright red fluorescent protein mScarlet-I into Escherichia coli Nissle 1917 ( EcN ). The engineered teLuc.FP-EcN can specifically target and colonize tumors without significant toxicity to the host. Acting as a continuous internal light source, teLuc.FP-EcN can activate the photosensitizer chlorin e6 (Ce6) to generate reactive oxygen species (ROS) and then effectively destroy tumor tissue from the inside. As a result, a significant reduction in tumor proliferation and extension of the overall survival in mouse tumor models has been observed. Furthermore, teLuc.FP-EcN-boosted PDT amplified its therapeutic effect by activating antitumor immune response, including the conversion of M2 macrophages into pro-inflammatory M1 macrophages, as well as an increase in the proportion of CD3 + T cells and a decrease in T-cell exhaustion. In conclusion, teLuc.FP-EcN can be used as an implantable light source for tumor phototherapy, which simultaneously possesses ROS generation and immune regulation.
Keyphrases
- photodynamic therapy
- escherichia coli
- reactive oxygen species
- fluorescence imaging
- immune response
- quantum dots
- signaling pathway
- dna damage
- cell death
- oxidative stress
- dna methylation
- sensitive detection
- dendritic cells
- drug delivery
- staphylococcus aureus
- wastewater treatment
- pseudomonas aeruginosa
- biofilm formation
- label free