期刊
ACS NANO
卷 12, 期 5, 页码 4503-4511出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.8b00763
关键词
intracellular delivery; nanosphere lithography; nanoneedle; gene delivery; drug delivery; nanorobotics; nanomotor
类别
资金
- National Science Foundation [CMMI-1636136]
- National Institutes of Health [R21EB016270]
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Training Program through its Clinical Fellowship Training Award Program
- Hyundai Hope on Wheels Foundation
- Alex's Lemonade Stand Foundation for Pediatric Cancer Research
- UCLA David Geffen School of Medicine Regenerative Medicine Theme Award
- Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA
- National Science Foundation of China [51603042]
- China Scholarship Council
- Royal Thai Government
An efficient nonviral platform for high-throughput and subcellular precision targeted intracellular delivery of nucleic acids in cell culture based on magnetic nanospears is reported. These magnetic nanospears are made of Au/Ni/Si (similar to 5 mu m in length with tip diameters <50 nm) and fabricated by nanosphere lithography and metal deposition. A magnet is used to direct the mechanical motion of a single nanospear, enabling precise control of position and three-dimensional rotation. These nanospears were further functionalized with enhanced green fluorescent protein (eGFP)-expression plasmids via a layer-by-layer approach before release from the underlying silicon substrate. Plasmid functionalized nanospears are guided magnetically to approach target adherent U87 glioblastoma cells, penetrating the delivery of the plasmid cargo. After 24 h, the target cell expresses green fluorescence indicating successful transfection. This nanospear-mediated transfection is readily scalable for the simultaneous manipulation of multiple cells using a rotating magnet. Cell viability >90% and transfection rates >80% were achieved, which exceed conventional nonviral intracellular methods. This approach is compatible with good manufacturing practices, circumventing barriers to the translation and clinical deployment of emerging cellular therapies.
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