Eliminating intratumoral bacteria with cGAS-STING-activating nanodrug-bacteria biohybrids potentiates cancer...

Area of Science:

• Oncology
• Microbiology
• Immunology
• Materials Science
• Nanotechnology

Background:

• Breast cancer is a major cause of female mortality.
• Intratumoral bacteria contribute to tumor immunosuppression.
• Targeted therapies for microbial influence in breast cancer are limited.

Purpose of the Study:

• To develop a novel nanodrug bacteria biohybrid system for breast cancer immunotherapy.
• To simultaneously eliminate immunosuppressive intratumoral bacteria and activate the cGAS-STING pathway.
• To suppress tumor progression through synergistic therapeutic strategies.

Main Methods:

• Development of a nanodrug bacteria biohybrid system: LGG-PDA@Cu-CPT, integrating Lactobacillus rhamnosus GG (LGG) probiotics, polydopamine (PDA), and copper-irinotecan (Cu-CPT) composites.
• Utilizing photothermal therapy (PTT) mediated by PDA for bacterial eradication and enhanced Cu2+ uptake.
• Activating the cGAS-STING pathway via CPT release and LGG, alongside bacterial remnants as immunostimulatory agents.

Main Results:

• PTT enhanced bacterial membrane disruption and Cu2+ uptake, leading to ROS generation and killing of Fusobacterium nucleatum (Fn).
• Elimination of Fn relieved the immunosuppressive tumor microenvironment.
• Activation of the cGAS-STING pathway triggered type I interferon production, dendritic cell maturation, and cytotoxic T lymphocyte infiltration, leading to immune-mediated tumor cell clearance.
• Synergistic bacterial elimination and cGAS-STING activation significantly enhanced anti-tumor immune responses and inhibited tumor progression.

Conclusions:

• The LGG-PDA@Cu-CPT system offers a promising synergistic strategy for breast cancer immunotherapy.
• Simultaneous bacterial elimination and cGAS-STING pathway activation effectively suppress tumor progression.
• This approach holds potential for a novel therapeutic strategy against breast cancer.