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LED-Based In Vitro Screening for Assessing Photoactivable Molecules in Bacterial Photodynamic Inactivation

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A Microrobotic System Based on Engineered Bacteria for Targeted Self-Driven Photodynamic Therapy.

Kai Jin¹, Lin Yu^1,2,3, Yue Zhang¹

¹Department of Environmental and Chemical Engineering, Shanghai University, Nanchen Rd. 333, Shanghai, China.

Angewandte Chemie (International Ed. in English)

|November 28, 2024

Summary

This study introduces a novel photodynamic therapy (PDT) platform using genetically modified E. coli to generate light, photosensitizers, and oxygen within tumors. This self-driven approach overcomes limitations for treating deep-seated tumors.

Keywords:

Microrobot Photodynamic therapy Synthetic biology Tumor therapy

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Area of Science:

Biotechnology
Oncology
Photodynamic Therapy

Background:

Photodynamic therapy (PDT) is clinically used for superficial tumors.
Inefficient delivery of light, photosensitizers, and oxygen limits PDT for deep-seated tumors.

Purpose of the Study:

To develop a novel platform for self-driven PDT in deep-seated tumors.
To overcome the limitations of external component delivery in traditional PDT.

Main Methods:

Genetically modified probiotic Escherichia coli (E. coli) to host three modules: Lux (light production), Hem1 (photosensitizer biosynthesis), and KatG (oxygen generation).
Utilized endogenous substrates within E. coli and tumors for self-driven photochemical reactions.
Tested the system's prolonged activity in vivo using mouse models.

Main Results:

The engineered E. coli system demonstrated prolonged activity for days in vivo.
The platform enabled metronomic PDT, which induced an immune response.
Successfully orchestrated endogenous generation of light, photosensitizer, and oxygen within tumors.

Conclusions:

The novel E. coli-based platform offers a self-driven approach to PDT.
This technology holds promise for revolutionizing PDT and treating deep-seated tumors.
Overcomes enduring challenges in PDT application for difficult-to-treat cancers.