A Logic AND-Gated Sonogene Nanosystem for Precisely Regulating the Apoptosis of Tumor Cells
A Logic AND-Gated Sonogene Nanosystem for Precisely Regulating the Apoptosis of Tumor Cells
复制标题
精确调控肿瘤细胞凋亡的逻辑与门控声基因纳米系统
DOI：
10.1021/acsami.0c13453
复制
发表时间：
2020-12-23
影响因子：
9.5
通讯作者：
Chang, Jin
中科院分区：
文献类型：
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作者：
Wang, Tiange;Wang, Hanjie;Chang, Jin
迄今为止，已经开发了许多诱导肿瘤细胞死亡的方法，例如使用化学药物和辐射。然而，它们都有一个共同的问题，即缺乏精确调节肿瘤细胞死亡的机制。它经常导致非特异性死亡和全身副作用。因此，这些传统方法的有效性和进一步应用受到限制。本文设计了一个逻辑与门控的声基因纳米系统，用于精确调控肿瘤细胞的凋亡。该系统的运行需要两个基本部分，MscL I92 L通道蛋白和超声。超声可以打开MscL I92 L蛋白通道，当其在细胞上表达时触发小分子通过通道的流入和流出。当通道长时间保持开放时，Ca 2+内流变得过量，这反过来激活了细胞的Ca'凋亡途径。MscL I92 L蛋白的表达与超声波的作用构成了逻辑与门，实现了对细胞凋亡的精确调控。这种策略将有助于减少非特异性触发和副作用。在该系统中，制备阳离子纳米脂质体作为载体，有效地将MscL I92 L质粒递送到体内肿瘤细胞。我们研究了该系统在不同肿瘤细胞系（HeLa，B16和4 T1）中的促凋亡作用。结果表明，B16细胞经6 MHz，15 W的持续超声作用30 min后，细胞凋亡率最高（早期凋亡率为11.9%，晚期凋亡率为59.1%）。该逻辑与门控声基因纳米系统有望为肿瘤治疗提供新的策略和发展方向。
To date, many methods have been developed for inducing tumor cell death, such as using chemical drugs and radiation. However, all of them have a common problem, a lack of mechanisms for precisely regulating the death of tumor cells. It often leads to nonspecific death and systemic side effects. Therefore, the efficacy and further application of these traditional methods are limited. In this paper, a logic AND-gated sonogene nanosystem was designed for precisely regulating the apoptosis of tumor cells. The running of this system required two essential parts, MscL I92L channel protein and ultrasound. Ultrasound could open the MscL I92L protein channel which when expressed on cells triggers the influx and outflux of small molecules through the channel. 'When the channel is kept open for a long time, Ca2+ influx becomes excessive which in turn activates the Ca' apoptosis pathway of cells. The expression of MscL I92L protein and the applying of ultrasound constituted the logic AND gate which could implement the precise regulation to apoptosis. This strategy would help reduce nonspecific triggers and side effects. In this system, cationic nanoliposomes were prepared as the carrier for effectively delivering MscL I92L plasmids to tumor cells in vivo. We investigated the apoptosis-promoting effect of this system in different tumor cell lines (HeLa, B16, and 4T1). The results demonstrated that the apoptosis rate was highest in the B16 cell line (the early apoptosis rate was 11.9% and the late apoptosis rate was 59.1%) when the cells were subjected to consistent ultrasound (6 MHz, 15 W) for 30 min. This logic AND-gated sonogene nanosystem is expected to provide a new strategy and development direction for tumor therapy.