Aptamer-functionalized targeted siRNA delivery system for tumor immunotherapy

Area of Science:

• Biomedical Engineering
• Cancer Research
• Immunotherapy

Background:

• Programmed death ligand 1 (PD-L1) overexpression on tumor cells promotes immune evasion.
• Reducing PD-L1 expression is a strategy to activate the immune system against tumors.
• RNA interference (RNAi) offers a method for gene regulation in cancer therapy.

Purpose of the Study:

• To construct a targeted siRNA delivery system (NPs@apt) for PD-L1 gene knockdown in non-small-cell lung carcinoma (A549) cells.
• To inhibit tumor immune evasion and promote anti-tumor immunity.
• To evaluate the efficacy and safety of the NPs@apt system in vitro.

Main Methods:

• NPs@apt system constructed by encapsulating PD-L1 siRNA with Lipofectamine 2000, fusing with erythrocyte membrane nanovesicles, and AS1411 aptamer modification.
• Erythrocyte membrane incorporation for reduced cytotoxicity and macrophage evasion.
• In vitro assessment of siRNA delivery, PD-L1 gene knockdown, T cell activation, and tumor cell growth inhibition.

Main Results:

• NPs@apt system demonstrated stability and effective protection of loaded siRNA.
• Selective delivery of PD-L1 siRNA into A549 cells was confirmed.
• Significant PD-L1 gene knockdown, enhanced T cell activation, and inhibited tumor cell growth were observed.

Conclusions:

• The developed NPs@apt system provides a targeted and effective strategy for siRNA delivery in cancer therapy.
• Erythrocyte membrane coating enhances biocompatibility and immune evasion of the delivery system.
• This approach holds promise for improving anti-tumor immunity by targeting PD-L1 expression.