School of Materials Science, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India.
J Phys Chem B. 2020 Jun 25;124(25):5323-5333. doi: 10.1021/acs.jpcb.0c03444. Epub 2020 Jun 16.
Polymer shelling around a nanoparticle is commonly employed for stabilization, surface chemistry, and bioconjugation. However, this shelling increases the overall size of the nanoparticle which limits many biomedical applications. Here we show that soft and nonionic polymer shelling can induce direct cytosolic delivery of a nanoparticle, as compared to clathrin-mediated uptake and lysozomal trafficking by a similarly sized nanoparticle with molecular shelling. Specifically, we have studied cellular internalization of two classes of colloidal nanoparticles of 10-50 nm hydrodynamic size. In one class, a 4-5 nm quantum dot is coated with a soft polyacrylate shell of varied thickness between 2 and 20 nm and in the other class a Au nanoparticle of varied size between 5 and 45 nm is coated with a molecular shell. We found that polymer shelling has two roles in controlling cellular internalization of nanoparticles. First, it increases the hydrodynamic size and controls the surface charge that influences the binding to the cell membrane, and 10 nm appears to be the minimum size requirement for such binding. Second, it increases softness that induces membrane penetration and directs cytosolic delivery of the nanoparticle. In particular, a soft and nonionic polymer shell induces lipid-raft-mediated direct cytosolic delivery, but a soft and cationic polymer shell induces clathrin-mediated endocytosis with lysozomal trafficking, like that of a nonionic molecular shell. The observed results can be used to design more effective nanoprobes for controlling intracellular processing.
聚合物壳层通常用于稳定、表面化学和生物偶联纳米粒子。然而，这种壳层增加了纳米粒子的总体尺寸，限制了许多生物医学应用。在这里，我们展示了软非离子聚合物壳层可以诱导纳米粒子的直接细胞质内递送，而相比之下，具有分子壳层的类似尺寸的纳米粒子通过网格蛋白介导的摄取和溶酶体运输。具体来说，我们研究了两类胶体纳米粒子的细胞内摄取，其水动力尺寸为 10-50nm。在一类中，4-5nm 的量子点被厚度在 2 到 20nm 之间的软聚丙烯酸酯壳层包覆，而在另一类中，尺寸在 5 到 45nm 之间的 Au 纳米粒子被分子壳层包覆。我们发现，聚合物壳层在控制纳米粒子的细胞内摄取中有两个作用。首先，它增加了水动力尺寸并控制了表面电荷，从而影响与细胞膜的结合，而 10nm 似乎是这种结合的最小尺寸要求。其次，它增加了柔软度，诱导了膜穿透，并指导了纳米粒子的细胞质内递送。特别是，软非离子聚合物壳层诱导脂筏介导的直接细胞质内递送，而软阳离子聚合物壳层诱导网格蛋白介导的内吞作用和溶酶体运输，类似于非离子分子壳层。观察到的结果可用于设计更有效的纳米探针来控制细胞内处理。
