Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer

Abstract Background PD‐1/PD‐L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐SiRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were construct...

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Main Authors: Guixue Yang, Dong Zhou, Yin Dai, Yanqi Li, Jiang Wu, Quanxing Liu, Xufeng Deng
Format: Article
Language:English
Published: Wiley 2022-11-01
Series:Thoracic Cancer
Subjects:
Online Access:https://doi.org/10.1111/1759-7714.14618
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author Guixue Yang
Dong Zhou
Yin Dai
Yanqi Li
Jiang Wu
Quanxing Liu
Xufeng Deng
author_facet Guixue Yang
Dong Zhou
Yin Dai
Yanqi Li
Jiang Wu
Quanxing Liu
Xufeng Deng
author_sort Guixue Yang
collection DOAJ
description Abstract Background PD‐1/PD‐L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐SiRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer in this study. Method In this study, PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐siRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer and functional evaluation was conducted. Results On the basis of the construction of the composite nano‐drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV‐PEI‐LNP were tested in vitro, and the downregulation effect of PD‐L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non‐small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy. Conclusion Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD‐L1, realizing the tumor‐specific expression of immune‐stimulating cytokines, which is a highly efficient and safe targeted therapy nano‐vaccine.
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spelling doaj.art-5e9a8b54a38145c2801c0dfc004ae6002022-12-22T02:38:55ZengWileyThoracic Cancer1759-77061759-77142022-11-0113212941295010.1111/1759-7714.14618Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancerGuixue Yang0Dong Zhou1Yin Dai2Yanqi Li3Jiang Wu4Quanxing Liu5Xufeng Deng6Department of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Information, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaDepartment of Thoracic Surgery, Xinqiao Hospital Army Medical University (Third Military Medical University) Chongqing ChinaAbstract Background PD‐1/PD‐L1 tumor immunotherapy shows effective anticancer in treatment of solid tumors, so PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐SiRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer in this study. Method In this study, PEI lipid nanoparticles (PEI‐LNP)/siRNA complex (EPV‐PEI‐LNP‐siRNA) with the therapeutic function of PD‐L1‐siRNA and EGFR short peptide/PD‐L1 double immune‐enhancing function were constructed for the prevention and treatment of EGFR‐positive lung cancer and functional evaluation was conducted. Results On the basis of the construction of the composite nano‐drug delivery system, the binding capacity, cytotoxicity, apoptosis and uptake capacity of siRNA and EPV‐PEI‐LNP were tested in vitro, and the downregulation effect of PD‐L1 on A549 cancer cells and the cytokine levels of cocultured T cells were tested. Lipid nanoparticles delivered siRNA and EGFR short peptide vaccine to non‐small cell lung cancer (NSCLC), increasing tumor invasion and activation of CD8 + T cells. Combination therapy is superior to single target therapy. Conclusion Our constructed lipid nanoparticles of tumor targeted therapy gene siRNA combination had the ability to target cells in vitro and downregulate the expression of PD‐L1, realizing the tumor‐specific expression of immune‐stimulating cytokines, which is a highly efficient and safe targeted therapy nano‐vaccine.https://doi.org/10.1111/1759-7714.14618lung cancerPEI‐EGFR‐PD‐L1‐siRNAtherapyvaccine
spellingShingle Guixue Yang
Dong Zhou
Yin Dai
Yanqi Li
Jiang Wu
Quanxing Liu
Xufeng Deng
Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
Thoracic Cancer
lung cancer
PEI‐EGFR‐PD‐L1‐siRNA
therapy
vaccine
title Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
title_full Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
title_fullStr Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
title_full_unstemmed Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
title_short Construction of PEI‐EGFR‐PD‐L1‐siRNA dual functional nano‐vaccine and therapeutic efficacy evaluation for lung cancer
title_sort construction of pei egfr pd l1 sirna dual functional nano vaccine and therapeutic efficacy evaluation for lung cancer
topic lung cancer
PEI‐EGFR‐PD‐L1‐siRNA
therapy
vaccine
url https://doi.org/10.1111/1759-7714.14618
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