DNAzyme-Assisted Nano-Herb Delivery System for Multiple Tumor Immune Activation.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunotherapy

Background:

• Immunotherapy faces challenges in solid tumors, necessitating novel strategies.
• Immune checkpoint blockade, targeting the PD1-PD-L1 axis, shows promise but requires enhancement.
• Combination therapies offer potential for improved antitumor efficacy.

Purpose of the Study:

• To develop a multifunctional nanosystem for combined gene therapy and immunotherapy.
• To enhance tumor targeting and immune activation in the tumor microenvironment.
• To provide supporting evidence for advanced antitumor therapies.

Main Methods:

• A pH/glutathione-responsive hollow manganese dioxide (H-MnO2) nanosystem was engineered.
• The nanosystem was loaded with DNAzyme and glycyrrhizic acid (GA), and modified with chlorine6 (Ce6).
• Biodegradation of H-MnO2 released Mn2+ ions for PD-L1 mRNA targeting and cGAS-STING pathway activation.

Main Results:

• The nanosystem demonstrated efficient delivery of DNAzyme and GA, enhancing tumor targeting.
• Released Mn2+ ions activated gene therapy by targeting PD-L1 mRNA and stimulated the cGAS-STING pathway.
• Ce6 and GA induced immunogenic cell death via reactive oxygen species generation.

Conclusions:

• The developed nanosystem offers a versatile strategy for targeted gene inhibition and immune pathway activation.
• This approach holds significant value for advancing potential immunotherapies against solid tumors.
• The study supports the development of combination therapies for enhanced cancer treatment.