Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma

Area of Science:

• Biomedical Engineering
• Immunology
• Nanotechnology

Background:

• Tumors employ immune escape mechanisms, hindering effective anti-cancer immunity.
• The PDL1/Pbrm1 gene axis is linked to poor response to immune checkpoint blockade (ICB) therapy.

Purpose of the Study:

• To develop a multifunctional nanocarrier for combined gene silencing and immune checkpoint inhibition.
• To enhance anti-tumor immune responses and overcome tumor immune escape.

Main Methods:

• A biomimetic nanocarrier (siRNA-CaP@PD1-NVs) was engineered for co-delivery.
• The nanocarrier targets PD1/PDL1 axis blockade and Pbrm1/PDL1 gene silencing.

Main Results:

• The nanocarrier significantly improved the tumor immunosuppressive microenvironment.
• Enhanced dendritic cell (DC) maturation, CD8+ T cell infiltration, and activity were observed.
• Effective tumor growth inhibition, prevention of recurrence, and metastasis were achieved.

Conclusions:

• The developed nanocarrier offers a potent strategy for co-delivery of siRNA, immune adjuvants, and ICB agents.
• This approach holds significant promise for improving immunotherapy effectiveness and safety.