ArticleCurrent gene therapy2021
Cytoplasmic Trafficking of Nanoparticles Delivers Plasmid DNA for Macrophage Gene-editing.
Article in Current gene therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization.Scientific reports · 2022Article
- Targeting of sialoadhesin-expressing macrophages through antibody-conjugated (polyethylene glycol) poly(lactic-co-glycolic acid) nanoparticles.Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology · 2022Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundSuccessful delivery of gene-editing tools using nano-carriers is dependent on the ability of nanoparticles to pass through the cellular membrane, move through the cytoplasm, and cross the nuclear envelope to enter the nucleus. It is critical that intracellular nanoparticles interact with the cytoskeletal network to move toward the nucleus, and must escape degradation pathways including lysosomal digestion. Without efficient intracellular transportation and nuclear entry, nanoparticles-based gene-editing cannot be effectively used for targeted genomic modification.
objectiveWe have developed nanoparticles with a low molecular weight branched polyethylenimine lipid shell and a PLGA core that can effectively deliver plasmid DNA to macrophages for gene editing while limiting toxicity.
methodsCore-shell nanoparticles were synthesized by a modified solvent evaporation method and were loaded with plasmid DNA. Confocal microscopy was used to visualize the internalization, intracellular distribution and cytoplasmic transportation of plasmid DNA loaded nanoparticles (pDNA-NPs) in bone marrow-derived macrophages.
resultsCore-shell nanoparticles had a high surface charge of +56 mV and narrow size distribution. When loaded with plasmid DNA for transfection, the nanoparticles increased in size from 150 nm to 200 nm, and the zeta potential decreased to +36 mV, indicating successful encapsulation. Further, fluorescence microscopy revealed that pDNA-NPs crossed the cell membrane and interacted with actin filaments. Intracellular tracking of pDNA-NPs showed successful separation of pDNA- NPs from lysosomes, allowing entry into the nucleus at 2 hours, with further nuclear ingress up to 5 hours. Bone marrow-derived macrophages treated with pDNA/GFP-NPs exhibited high GFP expression with low cytotoxicity.
conclusionTogether, this data suggests pDNA-NPs are an effective delivery system for macrophage gene-editing.
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Registered trials
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