Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism.
Aspect ratio determines the quantity of mesoporous silica nanoparticle uptake by a small GTPase-dependent macropinocytosis mechanism.
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纵横比决定了小小的GTPase依赖性大型细胞增多症机制的介孔二氧化硅纳米颗粒摄取的量。
DOI：
10.1021/nn103344k
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发表时间：
2011-06-28
期刊：
影响因子：
17.1
通讯作者：
Nel AE
中科院分区：
文献类型：
--
作者：
Meng H;Yang S;Li Z;Xia T;Chen J;Ji Z;Zhang H;Wang X;Lin S;Huang C;Zhou ZH;Zink JI;Nel AE
尽管工程纳米材料 (ENM) 的长宽比 (AR) 是决定生物学结果的关键物理化学参数之一，但人们对 AR 如何影响生物学结果了解甚少。通过使用覆盖一系列不同长度的介孔二氧化硅纳米颗粒 (MSNP) 文库，我们可以证明杆状颗粒的 AR 决定了 HeLa 和 A549 癌细胞系中巨胞饮过程摄取 MSNP 的速率和丰度。与较短或较长长度的棒相比，AR 为 2.1-2.5 的 MSNP 通过对阿米洛利、细胞松弛素 D、叠氮化物和 4 °C 抑制敏感的过程被大量吸收。具有中间 AR 的视杆细胞还诱导最大数量的丝状伪足、肌动蛋白聚合和小 GTP 结合蛋白（例如 Rac1、CDC42）的激活，这些蛋白涉及肌动蛋白细胞骨架的组装和丝状伪足的形成。当评估 AR 在紫杉醇或喜树碱递送中的作用时，AR 2.1-2.5 的杆对于药物递送和在 HeLa 细胞中产生细胞毒性杀伤显然更有效。综合考虑，我们的数据表明，HeLa 和 A549 细胞能够通过主动传感机制检测 MSNP 中的 AR 差异，从而可以利用加速巨胞饮作用来实现更有效的药物递送。
Although the aspect ratio (AR) of engineered nanomaterials (ENMs) is one of the key physicochemical parameters that could determine biological outcome, not much is understood about how AR contributes to shaping biological outcome. By using a mesoporous silica nanoparticle (MSNP) library that has been constructed to cover a range of different lengths, we could demonstrate that the AR of rod-shaped particles determine the rate and abundance of MSNP uptake by a macropinocytosis process in HeLa and A549 cancer cell lines. MSNPs with an AR of 2.1–2.5 were taken up in larger quantities compared to shorter or longer length rods by a process that is sensitive to amiloride, cytochalasin D, azide and 4 °C inhibition. The rods with intermediary AR also induced the maximal number of filopodia, actin polymerization and activation of small GTP-binding proteins (e.g. Rac1, CDC42) that involve assembly of the actin cytoskeleton and filopodia formation. When assessing the role of AR in the delivery of paclitaxel or camptothecin, the rods with AR 2.1–2.5 were clearly more efficient for drug delivery and generation of cytotoxic killing in HeLa cells. All considered, our data suggest an active sensoring mechanism by which HeLa and A549 cells are capable of detecting AR differences in MSNP to the extent that accelerated macropinocytosis can be used to achieve more efficient drug delivery.
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影响因子：
2.9
作者：
Arnold, M;Cavalcanti-Adam, EA;Spatz, JP
通讯作者：
Spatz, JP
影响因子：
10.8
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Champion, Julie A.;Katare, Yogesh K.;Mitragotri, Samir
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影响因子：
3.3
作者：
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Ghandehari, Hamidreza
影响因子：
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通讯作者：
Mitragotri S
影响因子：
9.2
作者：
Butler, B;Gao, CL;Blystone, SD
通讯作者：
Blystone, SD