Department of Medical Imaging, Jinling Hospital, School of Medicine, Nanjing University , Nanjing, 210002 Jiangsu, P. R. China.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing, 210093 Jiangsu, P. R. China.
J Am Chem Soc. 2018 Jan 31;140(4):1385-1393. doi: 10.1021/jacs.7b10694. Epub 2018 Jan 3.
Mesoporous solids have been widely used in various biomedical areas such as drug delivery and tumor therapy. Although deformability has been recognized as a prime important characteristic influencing cellular uptake, the synthesis of deformable mesoporous solids is still a great challenge. Herein, deformable thioether-, benzene-, and ethane-bridged hollow periodic mesoporous organosilica (HPMO) nanocapsules have successfully been synthesized for the first time by a preferential etching approach. The prepared HPMO nanocapsules possess uniform diameters (240-310 nm), high surface areas (up to 878 m·g), well-defined mesopores (2.6-3.2 nm), and large pore volumes (0.33-0.75 m·g). Most importantly, the HPMO nanocapsules simultaneously have large hollow cavities (164-270 nm), thin shell thicknesses (20-38 nm), and abundant organic moiety in the shells, which endow a lower Young's modulus (E) of 3.95 MPa than that of solid PMO nanoparticles (251 MPa). The HPMOs with low E are intrinsically flexible and deformable in the solution, which has been well-characterized by liquid cell electron microscopy. More interestingly, it is found that the deformable HPMOs can easily enter into human breast cancer MCF-7 cells via a spherical-to-oval morphology change, resulting in a 26-fold enhancement in cellular uptake (43.1% cells internalized with nanocapsules versus 1.65% cells with solid counterparts). The deformable HPMO nanocapsules were further loaded with anticancer drug doxorubicin (DOX), which shows high killing effects for MCF-7 cells, demonstrating the promise for biomedical applications.
介孔固体在药物输送和肿瘤治疗等多个生物医学领域得到了广泛应用。尽管变形性已被认为是影响细胞摄取的重要特征，但可变形介孔固体的合成仍然是一个巨大的挑战。在此，首次通过优先蚀刻方法成功合成了可变形的硫醚、苯和乙烷桥联的中空周期性介孔有机硅纳米胶囊。所制备的 HPMO 纳米胶囊具有均匀的直径（240-310nm）、高的比表面积（高达 878m·g）、明确的介孔（2.6-3.2nm）和大的孔体积（0.33-0.75m·g）。最重要的是，HPMO 纳米胶囊同时具有大的中空腔（164-270nm）、薄的壳厚度（20-38nm）和丰富的壳中的有机部分，使其杨氏模量（E）低至 3.95MPa，低于实心 PMO 纳米颗粒（251MPa）。具有低 E 的 HPMO 本质上是灵活且可变形的，这已通过液体细胞电子显微镜得到了很好的表征。更有趣的是，发现可变形的 HPMO 可以很容易地通过球形到椭圆形的形态变化进入人乳腺癌 MCF-7 细胞，从而使细胞摄取量增加 26 倍（纳米胶囊进入 43.1%的细胞，而实心纳米胶囊只有 1.65%）。可变形的 HPMO 纳米胶囊进一步负载了抗癌药物阿霉素（DOX），对 MCF-7 细胞显示出高杀伤作用，为生物医学应用展示了前景。
