Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.
Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.
复制标题
DOI：
10.1038/nmat4249
复制
发表时间：
2015-05
期刊：
影响因子：
41.2
通讯作者：
Tasciotti E
中科院分区：
文献类型：
--
作者：
Chiappini C;De Rosa E;Martinez JO;Liu X;Steele J;Stevens MM;Tasciotti E
将核酸受控输送到选定的组织仍然是一个低效的过程，存在以下问题：低的转染率，由于细胞类型和位置的不同而导致的可扩展性差，以及由于所使用的典型材料和程序引起的毒性问题而导致的安全性问题。利用纳米针在细胞内传递核酸已被证明是高效和最小的毒性，然而将这些特性扩展到体内传递一直是困难的，因为目前的接口策略依赖于复杂的设备或通过长时间的接口来主动的细胞内化。在这里，我们展示了通过金属辅助化学刻蚀硅制备的可生物降解的纳米针阵列可以进入胞浆以超过90%的效率共同传递DNA和siRNA，并且在体内纳米针可以导入血管内皮生长因子-165基因，在肌肉的靶区诱导持续的新生血管和局部6倍的血液灌注量增加。
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.