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Development of a Self-Luminescent Living Bioreactor for Enhancing Photodynamic Therapy in Breast Cancer.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2024 Aug 21; Vol. 35 (8), pp. 1269-1282. Date of Electronic Publication: 2024 Aug 09. - Publication Year :
- 2024
-
Abstract
- 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 <superscript>+</superscript> 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.
- Subjects :
- Animals
Female
Mice
Humans
Reactive Oxygen Species metabolism
Chlorophyllides
Mice, Inbred BALB C
Porphyrins chemistry
Porphyrins pharmacology
Porphyrins therapeutic use
Cell Line, Tumor
Escherichia coli drug effects
Photochemotherapy methods
Breast Neoplasms drug therapy
Breast Neoplasms therapy
Photosensitizing Agents therapeutic use
Photosensitizing Agents pharmacology
Photosensitizing Agents chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 35
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 39120495
- Full Text :
- https://doi.org/10.1021/acs.bioconjchem.4c00334