Engineered Bacteria for Enhanced Radiotherapy against Breast Carcinoma

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Radiotherapy is a cornerstone of cancer treatment but can damage surrounding healthy tissues.
• Tumor cells often develop resistance to radiation, limiting treatment efficacy.
• There is a need for strategies to enhance radiotherapy sensitivity and reduce side effects.

Purpose of the Study:

• To develop an integrated nanosystem (Bac@BNP) for sensitizing radiotherapy.
• To engineer bacteria to target tumors and modify the cell cycle for radiosensitivity.
• To utilize bismuth sulfide nanoparticles (BNPs) as radiosensitizers released within the tumor microenvironment.

Main Methods:

• Engineered bacteria (Bac) were designed to overexpress cytolysin A (ClyA) for cell cycle regulation.
• Peptide-modified bismuth sulfide nanoparticles (BNPs) were attached to the engineered bacteria.
• The nanosystem was designed to release BNPs in response to matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment.
• The combined system (Bac@BNP) was tested with X-ray irradiation on breast carcinoma models.

Main Results:

• The engineered bacteria (Bac) successfully targeted and colonized tumor sites.
• BNPs were released in response to the tumor microenvironment, acting as radiosensitizers.
• BNPs enhanced radiotherapy sensitivity by increasing reactive oxygen species (ROS) generation and DNA damage.
• The Bac@BNP system combined with X-ray irradiation significantly suppressed breast carcinoma growth in murine models.
• Reduced side effects were observed in the treated murine models.

Conclusions:

• The integrated Bac@BNP nanosystem effectively sensitizes tumors to radiotherapy.
• This approach offers a promising strategy for improving cancer treatment outcomes.
• The targeted delivery and responsive release mechanism minimize damage to healthy tissues, reducing side effects.