NatureMaterials：新方法使納米顆粒成功進入細胞

當將條紋狀的不同配合基以彼此相間的方式覆蓋在納米顆粒表面時，這種納米顆粒就可以直接穿入細胞而不會在細胞上留下洞穴，從而不會引起細胞的死亡，新成果日前發表在在線出版的《自然—材料學》(Nature Materials)期刊上。在未來的治療中，可以用這種方法將生物活性的分子送入細胞中。

細胞膜具有高度的防御能力，不會讓外界物質輕易進入。盡管也有部分生物分子能穿越細胞膜進入細胞之中，但具有類似大小的人工合成分子是否也能穿越細胞呢?曾有一段時間，學術界在這個問題上有相當的爭論。通常，人工合成分子只能進入細胞中一個有限制的特定小區域，而不是細胞質溶液中。對于像帶正電荷的納米顆粒來說，它們進入細胞時會在細胞膜上產生出一個小小的過渡性洞穴，即使這樣也會使細胞膜破裂，導致細胞死亡。

Francesco Stellacci和同事發現，黃金納米顆粒能夠穿越細胞膜不會導致細胞膜破裂，而且，如果以彼此間隔的形式在這種納米顆粒表面涂上負電荷配合基和疏水配合基，那么它們還能進入細胞液中。如果這些配合基在納米顆粒表面是隨意排列的，那么即使是涂上相同數量的配合基，這些顆粒也不能直接穿過細胞膜。(生物谷Bioon.com)

Nature Materials，7, 588 - 595，Ayush Verma，Francesco Stellacci

Surface-structure-regulated cell-membrane penetration by monolayer-protected nanoparticles

Ayush Verma¹, Oktay Uzun¹, Yuhua Hu², Ying Hu¹, Hee-Sun Han³, Nicki Watson⁴, Suelin Chen¹, Darrell J. Irvine^1,5 & Francesco Stellacci¹

Nanoscale objects are typically internalized by cells into membrane-bounded endosomes and fail to access the cytosolic cell machinery. Whereas some biomacromolecules may penetrate or fuse with cell membranes without overt membrane disruption, no synthetic material of comparable size has shown this property yet. Cationic nano-objects pass through cell membranes by generating transient holes, a process associated with cytotoxicity. Studies aimed at generating cell-penetrating nanomaterials have focused on the effect of size, shape and composition. Here, we compare membrane penetration by two nanoparticle 'isomers' with similar composition (same hydrophobic content), one coated with subnanometre striations of alternating anionic and hydrophobic groups, and the other coated with the same moieties but in a random distribution. We show that the former particles penetrate the plasma membrane without bilayer disruption, whereas the latter are mostly trapped in endosomes. Our results offer a paradigm for analysing the fundamental problem of cell-membrane-penetrating bio- and macro-molecules.