Synergistic Entry of Individual Nanoparticles into Mammalian Cells Driven by Free Energy Decline and Regulated by Their Sizes.
Synergistic Entry of Individual Nanoparticles into Mammalian Cells Driven by Free Energy Decline and Regulated by Their Sizes.
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DOI：
10.1021/acsnano.1c11068
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发表时间：
2022-03
期刊：
影响因子：
17.1
通讯作者：
Yushuang Wei;Haibo Chen;Yueling Li;Kejie He;Kai Yang;Hong‐Bo Pang
中科院分区：
文献类型：
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作者：
Yushuang Wei;Haibo Chen;Yueling Li;Kejie He;Kai Yang;Hong‐Bo Pang
细胞进入是纳米材料应用的常见先决条件之一。尽管对同质纳米颗粒（NP）组进行了广泛的研究，但对两种或多种类型的纳米颗粒共同给药时进行的研究较少。我们之前描述了两个异质 NP 组的协同细胞进入过程，其中用 TAT（转录反式激活因子）肽（T-NP）功能化的 NP 刺激细胞摄取共同施用的未功能化 NP（旁观者 NP、B-NP）。在这里，我们表明 NP 的协同细胞进入是由自由能下降驱动的，并且取决于 B-NP 的大小。模拟表明，当最初单独放置时，两个纳米粒子首先向彼此移动，而不是单独启动细胞进入。只有 T-NP 会引起膜向内弯曲，模拟内吞作用，从而将附近的 NP 吸引到同一个“囊泡”中。当两个纳米粒子靠近直至接触时，整个系统发生两相自由能下降，这可能是协同纳米粒子共进入的热力学驱动因素。通过实验，我们发现T-NPs增加了B-NPs与质膜的表观亲和力，这表明T-NPs有助于B-NPs“捕获”在内吞囊泡中。接下来，我们改变 B-NP 的尺寸，发现旁观者活动在 50 nm 左右达到峰值。模拟还表明，B-NP 的尺寸影响自由能下降，从而影响 NP 共入的趋势和动态。这些努力提供了一个系统，可以在生物物理基础上进一步了解单个纳米颗粒或多种纳米颗粒类型之间的协同细胞进入，并为细胞内递送纳米结构的未来设计提供线索。
Cell entry is one of the common prerequisites for nanomaterial applications. Despite extensive studies on a homogeneous group of nanoparticles (NPs), fewer studies have been performed when two or more types of NPs were coadministrated. We previously described a synergistic cell entry process for two heterogeneous groups of NPs, where NPs functionalized with TAT (transactivator of transcription) peptide (T-NPs) stimulate the cellular uptake of coadministered unfunctionalized NPs (bystander NPs, B-NPs). Here, we show that the synergistic cell entry of NPs is driven by free energy decline and depends on B-NP sizes. Simulations showed that when separately placed initially, two NPs first move toward each other instead of initiating cell entry individually. Only T-NP invokes an inward bending of membrane mimicking endocytosis, which attracts the nearby NPs into the same "vesicle". A two-phase free energy decline of the entire system occurred as two NPs get closer until contact, which is likely the thermodynamic driver for synergistic NP coentry. Experimentally, we found that T-NPs increase the apparent affinity of B-NPs to plasma membrane, suggesting that T-NPs help B-NPs "trapped" in the endocytic vesicles. Next, we varied the sizes of B-NPs and found that bystander activity peaks around 50 nm. Simulations also showed that the size of B-NPs influences the free energy decline, and thus the tendency and dynamics of NP coentry. These efforts provide a system to further understand the synergistic cell entry among individual NPs or multiple NP types on a biophysical basis and shed light on the future design of nanostructures for intracellular delivery.