Self-Assembled Nanoparticles Prepared from Low-Molecular-Weight PEI and Low-Generation PAMAM for EGFRvIII-Chimeric Antigen Receptor Gene Loading and T-Cell Transient Modification

International Journal of Nanomedicine
Qianru YuJinliang Peng

Abstract

The complex preparation procedures and severe toxicities are two major obstacles facing the wide use of chimeric antigen receptor-modified T (CAR-T) cells in clinical cancer immunotherapy. The nanotechnology-based T cell temporary CAR modification may be a potential approach to solve these problems and make the CAR-T cell-based tumor therapy feasible and broadly applicable. A series of plasmid DNA-loaded self-assembled nanoparticles (pDNA@SNPsx/y) prepared from adamantane-grafted polyamidoamine (Ad-PAMAM) dendrimers of different generations (G1 or G5) and cyclodextrin-grafted branched polyethylenimine (CD-PEI) of different molecular weights (800, 2000, or 25,000 Da) were characterized and evaluated. The detailed physicochemical properties, cellular interaction, and cytotoxicity of selected pDNA@SNPG1/800 were systematically investigated. Thereafter, the epidermal growth factor receptor variant III (EGFRvIII) CAR-expression plasmid vector (pEGFRvIII-CAR) was constructed and encapsulated into SNPG1/800. The resulting pEGFRvIII-CAR@SNPG1/800 was used for Jurkat cell transient transfection, and the EGFRvIII-CAR expressed in transfected cells was measured by flow cytometry and Western blot. Finally, the response of EGFRvIII CAR-posi...Continue Reading

Citations

Jan 8, 2021·Frontiers in Immunology·Wei LiMin Cui
Feb 10, 2021·Cancer Gene Therapy·Vinoth-Kumar LakshmananSalem Chouaib
Apr 4, 2021·International Journal of Molecular Sciences·Piotr Tarach, Anna Janaszewska
Apr 17, 2021·Advanced Materials·Arun R K KumarAndy Tay
Apr 30, 2021·Drug and Chemical Toxicology·Barbara ZiembaIda Franiak-Pietryga
Aug 14, 2020·Accounts of Chemical Research·Ian I CardleSuzie H Pun
Aug 29, 2021·Pharmaceutics·Giovanna C N B LôboSônia N Báo

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Methods Mentioned

BETA
xenograft
transfection
PBAE
genetic modification
flow cytometry
Electrophoresis
dynamic light scattering
Assay
nuclear magnetic resonance
transgenic

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