Yanheng Wu1, Wenyi Gu1, Jiang Li2, Chen Chen3, Zhi Ping Xu1. 1. Australian Institute for Bioengineering & Nanotechnology, University of Queensland, St Lucia, QLD 4072, Australia. 2. State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou, China. 3. School of Biomedical Sciences, Queensland Brain Institute, University of Queensland, St Lucia, QLD 4072, Australia.
Abstract
AIM: To determine if silencing PD-1 on tumor-infiltrating lymphocytes (TILs) and its ligand-1 (PD-L1) on cancer cells will enhance the cytotoxicity of TILs. MATERIALS & METHODS: Lipid-coated calcium phosphate nanoparticles were synthesized to deliver siRNAs against PD-1 and PD-L1 to TILs and breast cancer MCF-7 cells. The downregulation of PD-1/PD-L1 expressions was determined by real-time PCR and western blotting assays. The killing efficacy of TILs to MCF-7 cells was determined by cytotoxic T lymphocyte assay. RESULTS: Lipid-coated calcium phosphate nanoparticles effectively delivered siRNAs and silenced PD-1 and PD-L1sh expression. The knockdown of either gene or both greatly improved the cytotoxicity of TILs. CONCLUSION: Silencing PD-1 and PD-L1 is an effective approach to increase TIL cytotoxicity to cancer cells.
AIM: To determine if silencing PD-1 on tumor-infiltrating lymphocytes (TILs) and its ligand-1 (PD-L1) on cancer cells will enhance the cytotoxicity of TILs. MATERIALS & METHODS:Lipid-coated calcium phosphate nanoparticles were synthesized to deliver siRNAs against PD-1 and PD-L1 to TILs and breast cancer MCF-7 cells. The downregulation of PD-1/PD-L1 expressions was determined by real-time PCR and western blotting assays. The killing efficacy of TILs to MCF-7 cells was determined by cytotoxic T lymphocyte assay. RESULTS:Lipid-coated calcium phosphate nanoparticles effectively delivered siRNAs and silenced PD-1 and PD-L1sh expression. The knockdown of either gene or both greatly improved the cytotoxicity of TILs. CONCLUSION: Silencing PD-1 and PD-L1 is an effective approach to increase TIL cytotoxicity to cancer cells.
Authors: Mahmoud S Hanafy; Stephanie Hufnagel; Andrea N Trementozzi; Wedad Sakran; Jeanne C Stachowiak; John J Koleng; Zhengrong Cui Journal: AAPS PharmSciTech Date: 2021-01-31 Impact factor: 3.246