Tree-Udom Thapakorn, Seemork Jiraporn, Shigyou Kazuki, Hamada Tsutomu, Sangphech Naunpun, Palaga Tanapat, Insin Numpon, Pan-In Porntip, Wanichwecharungruang Supason
School of Materials Science, Japan Advanced Institute of Science and Technology , Nomi 923-1211, Japan.
ACS Appl Mater Interfaces. 2015 Nov 4;7(43):23993-4000. doi: 10.1021/acsami.5b06781. Epub 2015 Oct 26.
Although computer simulation and cell culture experiments have shown that elongated spherical particles can be taken up into cells more efficiently than spherical particles, experimental investigation on effects of these different shapes over the particle-membrane association has never been reported. Therefore, whether the higher cellular uptake of an elongated spherical particles is a result of a better particle-membrane association as suggested by some calculation works or a consequence of its influence on other cellular trans-membrane components involved in particle translocation process, cannot be concluded. Here, we study the effect of particle shape on the particle-membrane interaction by monitoring the association between particles of various shapes and lipid bilayer membrane of artificial cell-sized liposomes. Among the three shaped lanthanide-doped NaYF4 particles, all with high shape purity and uniformity, similar crystal phase, and surface chemistry, the elongated spherical particle shows the highest level of membrane association, followed by the spherical particle with a similar radius, and the hexagonal prism-shaped particle, respectively. The free energy of membrane curvature calculated based on a membrane indentation induced by a particle association indicates that among the three particle shapes, the elongated spherical particle give the most stable membrane curvature. The elongated spherical particles show the highest cellular uptake into cytosol of human melanoma (A-375) and human liver carcinoma (HepG2) cells when observed through a confocal laser scanning fluorescence microscope. Quantitative study using flow cytometry also gives the same result. The elongated spherical particles also possess the highest cytotoxicity in A-375 and normal skin (WI-38) cell lines, comparing to the other two shaped particles.
尽管计算机模拟和细胞培养实验表明，细长球形颗粒比球形颗粒更能有效地被细胞摄取，但从未有过关于这些不同形状对颗粒-膜结合影响的实验研究报道。因此，细长球形颗粒较高的细胞摄取量是如一些计算结果所表明的更好的颗粒-膜结合的结果，还是其对颗粒转运过程中涉及的其他细胞跨膜成分产生影响的结果，目前尚无定论。在此，我们通过监测各种形状的颗粒与人工细胞大小的脂质体的脂质双层膜之间的结合，研究颗粒形状对颗粒-膜相互作用的影响。在三种形状的镧系掺杂NaYF4颗粒中，它们均具有高形状纯度和均匀性、相似的晶相以及表面化学性质，其中细长球形颗粒表现出最高水平的膜结合，其次是半径相似的球形颗粒，最后是六棱柱形颗粒。基于颗粒结合引起的膜压痕计算得出的膜曲率自由能表明，在这三种颗粒形状中细长球形颗粒产生最稳定的膜曲率。通过共聚焦激光扫描荧光显微镜观察发现，细长球形颗粒在人黑色素瘤（A - 375）细胞和人肝癌（HepG2）细胞的胞质溶胶中表现出最高的细胞摄取量。使用流式细胞术进行的定量研究也得出了相同的结果。与其他两种形状的颗粒相比，细长球形颗粒在A - 375和正常皮肤（WI - 38）细胞系中也具有最高的细胞毒性。
