Engineered Bacterial Biohybrid-Mediated CD47-SIRPα Blockade and HSP90 Inhibition for Enhanced Immuno-Photothermal...

Area of Science:

• Biomedical Engineering
• Cancer Immunotherapy
• Nanomedicine

Background:

• Macrophage phagocytosis of tumor cells is a promising cancer treatment strategy.
• Tumor cells express antiphagocytic molecules like CD47, hindering this process.
• Simply reducing CD47 is insufficient; additional 'eat me' signals are needed.

Purpose of the Study:

• To develop an engineered bacterial biohybrid system (eVNP@AuNFs) for enhanced cancer therapy.
• To decrease CD47 and HSP90 protein expression in tumor cells.
• To achieve a combination therapy of immunotherapy and photothermal treatment.

Main Methods:

• Engineered attenuated Salmonella VNP20009 with CD47 and HSP90 shRNA plasmids.
• Adsorbed flower-like gold nanoparticle (AuNF) photothermal agents onto engineered bacteria.
• Administered eVNP@AuNF hybrid intravenously into 4T1 tumor-bearing mice.

Main Results:

• eVNP@AuNF hybrid selectively accumulated in tumor tissues.
• Reduced CD47 and HSP90 expression, enhancing macrophage phagocytosis.
• NIR-II laser irradiation induced immunogenic cell death and systemic antitumor immunity.

Conclusions:

• The eVNP@AuNF bacterial hybrid effectively eradicates primary tumors.
• This system elicits a systemic antitumor immune response, inhibiting tumor recurrence.
• Presents a novel hybrid system for hierarchical modulation of the tumor immune response.