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Modular-designed engineered bacteria for precision tumor immunotherapy via spatiotemporal manipulation by magnetic
Xiaotu Ma1,2,3, Xiaolong Liang2, Yao Li1,4
1CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing, 100190, China.
Nature Communications
|March 24, 2023
Summary
Engineered bacteria carrying magnetic nanoparticles are guided by magnetic fields to tumors. Upon heating, they release anti-CD47 nanobodies, activating immune responses for potent tumor treatment.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Immunotherapy
Background:
- Bacterial micro-nano biorobots show promise for cancer therapy.
- Precise control over bacterial gene expression and drug release is crucial to minimize toxicity.
Purpose of the Study:
- To develop magnetic field-controlled, bacteria-based nanobots for targeted cancer immunotherapy.
- To achieve spatiotemporal control over drug release and immune response activation in tumors.
Main Methods:
- Engineered Escherichia coli were modified with Fe3O4@lipid nanocomposites for magnetic manipulation.
- Bacteria accumulated in orthotopic colon tumors and were activated by an alternating magnetic field to generate heat.
- Heat triggered lysis protein expression, leading to bacterial lysis and release of pre-expressed anti-CD47 nanobodies.
Main Results:
- Magnetic nanoparticles enabled magnetic field-controlled bacterial motion and accumulation in tumors.
- Heat generated by magnetic fields initiated bacteria lysis and targeted drug release.
- The combination of bacterial lysate and anti-CD47 nanobody elicited robust innate and adaptive immune responses, reducing both primary and distal tumors.
Conclusions:
- Magnetic field manipulation allows for precise spatiotemporal control of gene expression and drug release from engineered bacteria.
- This approach enables targeted CD47 blockage and precision immunotherapy, demonstrating significant antitumor effects.
