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Ultrasound-assisted magnetic nanoparticle-based gene delivery.

ABSTRACT: Targeted gene delivery is important in biomedical research and applications. In this paper, we synergistically combine non-viral chemical materials, magnetic nanoparticles (MNPs), and a physical technique, low-intensity pulsed ultrasound (LIPUS), to achieve efficient and targeted gene delivery. The MNPs are iron oxide super-paramagnetic nanoparticles, coated with polyethyleneimine (PEI), which makes a high positive surface charge and is favorable for the binding of genetic materials. Due to the paramagnetic properties of the MNPs, the application of an external magnetic field increases transfection efficiency while LIPUS stimulation enhances cell viability and permeability. We found that stimulation at the intensity of 30 mW/cm2 for 10 minutes yields optimal results with a minimal adverse effect on the cells. By combining the effect of the external magnetic field and LIPUS, the genetic material (GFP or Cherry Red plasmid) can enter the cells. The flow cytometry results showed that by using just a magnetic field to direct the genetic material, the transfection efficiency on HEK 293 cells that were treated by our MNPs was 56.1%. Coupled with LIPUS stimulation, it increased to 61.5% or 19% higher than the positive control (Lipofectamine 2000). Besides, compared with the positive control, our method showed less toxicity. Cell viability after transfection was 63.61%, which is 19% higher than the standard transfection technique. In conclusion, we designed a new gene-delivery method that is affordable, targeted, shows low-toxicity, yet high transfection efficiency, compared to other conventional approaches.

SUBMITTER: Zhang W

PROVIDER: S-EPMC7514102 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Ultrasound-assisted magnetic nanoparticle-based gene delivery.

Zhang Wei W Abdelrasoul Gaser N GN Savchenko Oleksandra O Abdrabou Abdalla A Wang Zhixiang Z Chen Jie J

PloS one 20200924 9

Targeted gene delivery is important in biomedical research and applications. In this paper, we synergistically combine non-viral chemical materials, magnetic nanoparticles (MNPs), and a physical technique, low-intensity pulsed ultrasound (LIPUS), to achieve efficient and targeted gene delivery. The MNPs are iron oxide super-paramagnetic nanoparticles, coated with polyethyleneimine (PEI), which makes a high positive surface charge and is favorable for the binding of genetic materials. Due to the ...[more]

PMID: 32970723

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Project description:BackgroundThe characteristic progression of Lewy pathology in Parkinson's disease likely involves intercellular exchange and the accumulation of misfolded α-synuclein amplified by a prion-like self-templating mechanism. Silencing of the α-synuclein gene could provide long-lasting disease-modifying benefits by reducing the requisite substrate for the spreading aggregation.ObjectivesAs a result of the poor penetration of viral vectors across the blood-brain barrier, gene therapy for central nervous system disorders requires direct injections into the affected brain regions, and invasiveness is further increased by the need for bilateral delivery to multiple brain regions. Here we test a noninvasive approach by combining low-intensity magnetic resonance-guided focused ultrasound and intravenous microbubbles that can transiently increase the access of brain impermeant therapeutic macromolecules to targeted brain regions.MethodsTransgenic mice expressing human α-synuclein were subjected to magnetic resonance-guided focused ultrasound targeted to 4 brain regions (hippocampus, substantia nigra, olfactory bulb, and dorsal motor nucleus) in tandem with intravenous microbubbles and an adeno-associated virus serotype 9 vector bearing a short hairpin RNA sequence targeting the α-synuclein gene.ResultsOne month following treatment, α-synuclein immunoreactivity was decreased in targeted brain regions, whereas other neuronal markers such as synaptophysin or tyrosine hydroxylase were unchanged, and cell death and glial activation remained at basal levels.ConclusionsThese results demonstrate that magnetic resonance-guided focused ultrasound can effectively, noninvasively, and simultaneously deliver viral vectors targeting α-synuclein to multiple brain areas. Importantly, this approach may be useful to alter the progression of Lewy pathology along selected neuronal pathways, particularly as prodromal PD markers improve early diagnoses. © 2018 International Parkinson and Movement Disorder Society.

Dataset Information

Ultrasound-assisted magnetic nanoparticle-based gene delivery.

Publications

Ultrasound-assisted magnetic nanoparticle-based gene delivery.

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