Rock the nucleus: significantly enhanced nuclear membrane permeability and gene transfection by plasmonic nanobubble induced nanomechanical transduction
Rock the nucleus: significantly enhanced nuclear membrane permeability and gene transfection by plasmonic nanobubble induced nanomechanical transduction
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DOI：
10.1039/c7cc09613e
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发表时间：
2018-03-11
影响因子：
4.9
通讯作者：
Qin, Zhenpeng
中科院分区：
文献类型：
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作者：
Li, Xiuying;Kang, Peiyuan;Qin, Zhenpeng
对于许多生物分子，包括抗癌药物、蛋白质和DNA，有效地递送到细胞核仍然是一个重大挑战。尽管有许多尝试来改善核输入，包括使用核定位信号（NLS）肽和纳米颗粒载体，但它们受到纳米颗粒尺寸、缀合方法、对功能性核输入的依赖和细胞内运输机制的限制。为了克服这些限制，在这里，我们报告说，来自等离子体纳米气泡的纳米机械力增加了核膜的渗透性，并促进了大分子进入细胞核的普遍吸收，包括大于核孔复合物的大分子，否则不会进入细胞核。重要的是，我们表明，与单独的标准电穿孔处理相比，等离子体纳米气泡诱导的纳米机械转导显著提高了基因转染和蛋白质表达。这种新型的纳米机械转导增加了尺寸范围，并广泛适用于将大分子递送到细胞核，从而带来新的机会和应用，包括基因治疗和抗癌药物递送。
Efficient delivery to the cell nucleus remains a significant challenge for many biomolecules, including anticancer drugs, proteins and DNAs. Despite numerous attempts to improve nuclear import including the use of nuclear localization signal (NLS) peptides and nanoparticle carriers, they are limited by the nanoparticle size, conjugation method, dependence on the functional nuclear import and intracellular trafficking mechanisms. To overcome these limitations, here we report that the nanomechanical force from plasmonic nanobubbles increases nuclear membrane permeability and promotes universal uptake of macromolecules into the nucleus, including macromolecules that are larger than the nuclear pore complex and would otherwise not enter the nucleus. Importantly, we show that plasmonic nanobubble-induced nanomechanical transduction significantly improves gene transfection and protein expression, compared to standard electroporation treatment alone. This novel nanomechanical transduction increases the size range and is broadly applicable for macromolecule delivery to the cell nucleus, leading to new opportunities and applications including for gene therapy and anticancer drug delivery.