Chiappini C, De Rosa E, Martinez J O, Liu X, Steele J, Stevens M M, Tasciotti E
1] Department of Materials, Imperial College London, London, SW6 7PB, UK [2] Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London, SW6 7PB, UK.
Department of Nanomedicine, Houston Methodist Research Institute, Houston, Texas 77030, USA.
Nat Mater. 2015 May;14(5):532-9. doi: 10.1038/nmat4249. Epub 2015 Mar 30.
The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle.
将核酸可控地递送至选定组织仍然是一个效率低下的过程，受到低转染效率、因细胞类型和位置效率不同而导致的可扩展性差以及由于所采用的典型材料和程序引发的毒性问题而产生的安全性存疑等问题的困扰。使用纳米针进行核酸的细胞内递送已在体外显示出高效率和最小毒性，然而将这些特性扩展到体内递送却很困难，因为当前的接口策略依赖于复杂的设备或通过长时间接口实现的主动细胞内化。在这里，我们表明，通过金属辅助化学蚀刻硅制造的可调谐可生物降解纳米针阵列可以进入细胞质，以大于90%的效率共同递送DNA和siRNA，并且在体内，纳米针转染VEGF - 165基因，诱导持续的新血管形成，并使肌肉目标区域的局部血液灌注增加六倍。
