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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Aptamer-functionalized targeted siRNA delivery system for tumor immunotherapy
Haiyin Lv1,2, Tengfei Wang2, Fanshu Ma2
1School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, People's Republic of China.
Abstract:
Programmed death ligand 1 (PD-L1) overexpressed on the surface of tumor cells is one of the reasons for tumor immune escape. Reducing PD-L1 expression has been proved to be an effective strategy to facilitate immune system activation and inhibit tumor progression. RNA interference (RNAi) is a promising technology for gene regulation in tumor therapy. In this study, we constructed a targeted siRNA delivery system NPs@apt to transfect PD-L1 siRNA into human non-small-cell lung carcinoma cell line (A549) for inhibiting tumor immune evasion. NPs@apt was prepared by compressing PD-L1 siRNA with cationic Lipofectamine 2000, fusing with erythrocyte membrane-derived nanovesicles, and further modifying with targeting AS1411 aptamer. The introduction of erythrocyte membrane endowed the siRNA delivery system with lower cytotoxicity and the ability to escape from the phagocytosis of macrophages. The stability of NPs@apt and the protection to loaded siRNA were confirmed.In vitrostudies after NPs@apt treatment demonstrated that PD-L1 siRNA was selectively delivered into A549 cells, and further resulted in PD-L1 gene knockdown, T cell activation and tumor cell growth inhibition. This study offered an alternative strategy for specific siRNA transfection for improving anti-tumor immunity.
Insights
This study developed a targeted nanoparticle system (NPs@apt) to deliver siRNA, reducing PD-L1 expression in lung cancer cells. This approach enhances anti-tumor immunity by overcoming immune evasion.
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.
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