دورية أكاديمية
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Plasmid DNA cationic non-viral vector complexes induce cytotoxicity-associated PD-L1 expression up-regulation in cancer cells in vitro.

التفاصيل البيبلوغرافية
العنوان: Plasmid DNA cationic non-viral vector complexes induce cytotoxicity-associated PD-L1 expression up-regulation in cancer cells in vitro.
المؤلفون: Qin Y; Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK., Walters AA; Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK., Al-Jamal KT; Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: khuloud.al-jamal@kcl.ac.uk.
المصدر: International journal of pharmaceutics [Int J Pharm] 2023 Jan 25; Vol. 631, pp. 122481. Date of Electronic Publication: 2022 Dec 10.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 7804127 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3476 (Electronic) Linking ISSN: 03785173 NLM ISO Abbreviation: Int J Pharm Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Elsevier/North-Holland Biomedical Press.
مواضيع طبية MeSH: B7-H1 Antigen*/genetics , Neoplasms*, Up-Regulation ; Transfection ; Plasmids/genetics ; DNA ; Polyethyleneimine
مستخلص: Non-viral vectors are promising nucleic acid carriers which have been utilized in gene-based cancer immunotherapy. The aim of this study is to compare the transfection efficiency and cytotoxicity of three cationic non-viral vectors namely Polyethylenimine (PEI), Lipofectamine 2000 (LPF) and stable nucleic acid lipid particles (SNALPs) of different lipid compositions, for the delivery of plasmid DNA (pDNA) expressing immunostimulatory molecules, OX40L or 4-1BBL, to cancer cells in vitro. The results indicate that PEI and LPF are efficient vectors for pDNA delivery with high transfection efficiency obtained. However, pDNA-PEI and pDNA-LPF complexes up-regulated the expression of programmed death ligand-1 (PD-L1) and induced significant cytotoxicity in both B16F10 and CT26 cell lines. The up-regulation of PD-L1 expression induced by pDNA-PEI and pDNA-LPF complexes was independent of cancer cell line, nor was it linked to the presence of GpC motifs in the pDNA. In contrast, the use of biocompatible SNALPs (MC3 and KC2 types) resulted in lower pDNA transfection efficiency, however no significant up-regulation of PD-L1 or cytotoxicity was observed. A strong correlation was found between up-regulation of PD-L1 expression and cytotoxicity. Up-regulation of PD-L1 expression could be mitigated with RNAi, maintaining expression at basal levels. Due to the improved biocompatibility and the absence of PD-L1 up-regulation, SNALPs represent a viable non-viral nucleic acid vector for delivery of pDNA encoding immunostimulatory molecules. The results of this study suggest that PD-L1 expression should be monitored when selecting commercial transfection reagents as pDNA vectors for cancer immunotherapy in vitro.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Cancer cells; Cancer immunotherapy; Cationic non-viral vector; Cytotoxicity; Nanoparticles; PD-L1; plasmid DNA
المشرفين على المادة: 0 (CD274 protein, human)
0 (B7-H1 Antigen)
9007-49-2 (DNA)
9002-98-6 (Polyethyleneimine)
تواريخ الأحداث: Date Created: 20221213 Date Completed: 20230113 Latest Revision: 20230113
رمز التحديث: 20240628
DOI: 10.1016/j.ijpharm.2022.122481
PMID: 36513254
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-3476
DOI:10.1016/j.ijpharm.2022.122481