Casarrubios Laura, Gómez-Cerezo Natividad, Feito María José, Vallet-Regí María, Arcos Daniel, Portolés María Teresa
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), 28040 Madrid, Spain.
Departamento de Química en Ciencias Farmacéuticas, Facultad de Farmacia, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria Hospital 12 de Octubre i+12, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Nanomaterials (Basel). 2020 Dec 21;10(12):2573. doi: 10.3390/nano10122573.
The incorporation and effects of hollow mesoporous nanospheres in the system SiO-CaO (nanoMBGs) containing ipriflavone (IP), a synthetic isoflavone that prevents osteoporosis, were evaluated. Due to their superior porosity and capability to host drugs, these nanoparticles are designed as a potential alternative to conventional bioactive glasses for the treatment of periodontal defects. To identify the endocytic mechanisms by which these nanospheres are incorporated within the MC3T3-E1 cells, five inhibitors (cytochalasin B, cytochalasin D, chlorpromazine, genistein and wortmannin) were used before the addition of these nanoparticles labeled with fluorescein isothiocyanate (FITC-nanoMBGs). The results indicate that nanoMBGs enter the pre-osteoblasts mainly through clathrin-dependent mechanisms and in a lower proportion by macropinocytosis. The present study evidences the active incorporation of nanoMBG-IPs by MC3T3-E1 osteoprogenitor cells that stimulate their differentiation into mature osteoblast phenotype with increased alkaline phosphatase activity. The final aim of this study is to demonstrate the biocompatibility and osteogenic behavior of IP-loaded bioactive nanoparticles to be used for periodontal augmentation purposes and to shed light on internalization mechanisms that determine the incorporation of these nanoparticles into the cells.
评估了中空介孔纳米球在含有依普黄酮(IP)的SiO-CaO体系(纳米MBGs)中的掺入情况及其效果。依普黄酮是一种可预防骨质疏松的合成异黄酮。由于其优异的孔隙率和载药能力,这些纳米颗粒被设计为治疗牙周缺损的传统生物活性玻璃的潜在替代品。为了确定这些纳米球被MC3T3-E1细胞摄取的内吞机制,在用异硫氰酸荧光素标记的这些纳米颗粒(FITC-纳米MBGs)添加之前,使用了五种抑制剂(细胞松弛素B、细胞松弛素D、氯丙嗪、染料木黄酮和渥曼青霉素)。结果表明,纳米MBGs主要通过网格蛋白依赖性机制进入前成骨细胞,通过巨胞饮作用进入的比例较低。本研究证明了MC3T3-E1骨祖细胞对纳米MBG-IPs的主动摄取,这种摄取刺激它们分化为具有增加的碱性磷酸酶活性的成熟成骨细胞表型。本研究的最终目的是证明负载依普黄酮的生物活性纳米颗粒用于牙周增强目的的生物相容性和成骨行为,并阐明决定这些纳米颗粒进入细胞的内化机制。