Dipartmento di Scienze Chimiche e Geologiche, Università di Cagliari-CSGI and CNBS, Cittadella Universitaria, S.S. 554 bivio Sestu, 09042 Monserrato, CA, Italy.
Dipartimento di Scienze Biomediche, Università di Cagliari, Cittadella Universitaria, S.S. 554 bivio Sestu, 09042 Monserrato, CA, Italy.
Colloids Surf B Biointerfaces. 2018 Aug 1;168:50-59. doi: 10.1016/j.colsurfb.2018.02.019. Epub 2018 Feb 12.
Mesoporous silica nanoparticles (MSNs) were functionalized with amino groups (MSN-NH) and then with hyaluronic acid, a biocompatible biopolymer which can be recognized by CD44 receptors in tumor cells, to obtain a targeting drug delivery system. To this purpose, three hyaluronic acid samples differing for the molecular weight, namely HA (8-15 kDa), HA (30-50 kDa) and HA (90-130 kDa), were used. The MSN-HA, MSN-HA, and MSN-HA materials were characterized through zeta potential and dynamic light scattering measurements at pH = 7.4 and T = 37 °C to simulate physiological conditions. While zeta potential showed an increasing negative value with the increase of the HA chain length, an anomalous value of the hydrodynamic diameter was observed for MSN-HA, which was smaller than that of MSN-HA and MSN-HA samples. The cellular uptake of MSN-HA samples on HeLa cells at 37 °C was studied by optical and electron microscopy. HA chain length affected significantly the cellular uptake that occurred at a higher extent for MSN-NH and MSN-HA than for MSN-HA and MSN-HA samples. Cellular uptake experiments carried out at 4 °C showed that the internalization process was inhibited for MSN-HA samples but not for MSN-NH. This suggests the occurrence of two different mechanisms of internalization. For MSN-NH the uptake is mainly driven by the attractive electrostatic interaction with membrane phospholipids, while MSN-HA internalization involves CD44 receptors overexpressed in HeLa cells.
介孔硅纳米粒子（MSNs）被氨基官能化（MSN-NH），然后与透明质酸结合，透明质酸是一种生物相容性的生物聚合物，可以被肿瘤细胞中的 CD44 受体识别，从而获得靶向药物传递系统。为此，使用了三种分子量不同的透明质酸样品，即 HA（8-15 kDa）、HA（30-50 kDa）和 HA（90-130 kDa）。MSN-HA、MSN-HA 和 MSN-HA 材料在 pH = 7.4 和 T = 37°C 下通过动电电位和动态光散射测量进行了表征，以模拟生理条件。虽然动电电位随着 HA 链长的增加而呈现出越来越负的正值，但对于 MSN-HA 观察到了水动力直径的异常值，其小于 MSN-HA 和 MSN-HA 样品的值。在 37°C 下，通过光学和电子显微镜研究了 HeLa 细胞对 MSN-HA 样品的细胞摄取。HA 链长显著影响细胞摄取，MSN-NH 和 MSN-HA 对细胞摄取的影响大于 MSN-HA 和 MSN-HA 样品。在 4°C 下进行的细胞摄取实验表明，对于 MSN-HA 样品，内化过程被抑制，但对于 MSN-NH 则没有。这表明存在两种不同的内化机制。对于 MSN-NH，摄取主要是由与膜磷脂的吸引力静电相互作用驱动的，而 MSN-HA 的内化涉及 HeLa 细胞中过表达的 CD44 受体。
