肝素化介孔硅纳米粒子的合成及其抗肿瘤活性研究
发布时间：2019-06-16 17:55
【摘要】：在过去的20年里,纳米技术经历了快速的发展。由于介孔硅纳米粒子(MSNs)具有良好的物理-化学特性和生物相容性,因此它们曾被广泛应用于药物传递、药物靶向、基因转染和细胞追踪等各个方面。在过去的几十年里尽管基于功能化的MSNs的药物传递系统(DDSs)的体外研究取得了良好的结果,但有关这些功能化的以MSNs为基础的DDSs的生物安全性和治疗效果的体内评价近年来才刚刚开始。本文通过以下步骤进行研究:(1)首先,我们用溶胶-凝胶法合成了球形、粒径为120-160 nm、无序的介孔结构、分散性较好的氨基化介孔硅纳米粒子(MSNs-NH2);(2)其次,将功能性活性分子肝素共价结合在MSNs-NH2上形成肝素化介孔硅纳米粒子(MSNs-HP)。结果表明肝素在MSNs-NH2上的固定对其形态学并无影响,但MSNs-NH2的BET表面积、孔容、孔径和Zeta电位分别从552 cm2/g,0.74 cm3/g,2.58 nm,34 mV减少至329 cm2/g,0.40 cm3/g,2.07 nm,-43 mV,用甲苯胺蓝法测定MSNs-NH2对肝素的负载率约为2%(w/w);(3)然后,我们通过物理吸附法将阿霉素(DOX)负载到MSNs-HP上,并对DOX进行定量分析测得MSNs-HP对DOX的负载率为4%(w/w)。根据其体内和体外释放曲线,可以看出在起初的8 h内DOX出现突释,整个释放过程超过了70 h。将负载DOX的纳米粒子静脉注射后,DOX在血浆中的峰浓度可以维持6 h。结果表明MSNs-HP可以穿透进入癌细胞并且延缓抗癌药物DOX的释放,这有助于提高治疗效果。最后我们以H22移植鼠为动物实验模型对所合成的纳米粒子进行了体内评价,结果显示MSNs-HP在负载较少量药物的情况下就能与单独使用较大剂量的抗肿瘤药物产生类似的效果。负载DOX的MSNs-HP的肿瘤抑制率(58%)远远超过了在纳米粒子中的DOX的肿瘤抑制率(18%),并且与其大剂量(7倍剂量)的DOX的抑制率(67%)相近,这表明MSNs-HP的使用可以显著提高DOX的抗肿瘤效果。此外,我们发现这个系统比使用较大剂量的药物更加安全。这些因素可能会使MSNs-HP成为抗肿瘤药物传递的一种高效、低毒的载体。
[Abstract]:In the past 20 years, nanotechnology has experienced rapid development. Mesoporous silicon nanoparticles (MSNs) have been widely used in drug delivery, drug targeting, gene transfer and cell tracking because of their good physical-chemical properties and biocompatibility. In the past few decades, although the in vitro research of (DDSs), a drug delivery system based on functionalized MSNs, has achieved good results, the in vivo evaluation of the biosafety and therapeutic effect of these functionalized MSNs-based DDSs has only just begun in recent years. In this paper, the following steps have been studied: (1) firstly, the mesoporous silicon nanoparticles (MSNs-NH2); (2) with spherical mesoporous structure with particle size of 120 nm, and good dispersion were synthesized by sol-gel method. Secondly, the functional active molecular heparin was covalently combined on MSNs-NH2 to form heparin mesoporous silicon nanoparticles (MSNs-HP). The results showed that the fixation of heparin on MSNs-NH2 had no effect on its morphology, but the BET surface area, pore volume, pore size and Zeta potential of MSNs-NH2 decreased from 552 cm2/g,0.74 cm3/g,2.58 nm,34 mV to 329 cm2/g,0.40 cm3/g,2.07 nm,-43 mV,. The loading rate of MSNs-NH2 on heparin was about 2% (w 鈮，
本文编号：2500709
[Abstract]:In the past 20 years, nanotechnology has experienced rapid development. Mesoporous silicon nanoparticles (MSNs) have been widely used in drug delivery, drug targeting, gene transfer and cell tracking because of their good physical-chemical properties and biocompatibility. In the past few decades, although the in vitro research of (DDSs), a drug delivery system based on functionalized MSNs, has achieved good results, the in vivo evaluation of the biosafety and therapeutic effect of these functionalized MSNs-based DDSs has only just begun in recent years. In this paper, the following steps have been studied: (1) firstly, the mesoporous silicon nanoparticles (MSNs-NH2); (2) with spherical mesoporous structure with particle size of 120 nm, and good dispersion were synthesized by sol-gel method. Secondly, the functional active molecular heparin was covalently combined on MSNs-NH2 to form heparin mesoporous silicon nanoparticles (MSNs-HP). The results showed that the fixation of heparin on MSNs-NH2 had no effect on its morphology, but the BET surface area, pore volume, pore size and Zeta potential of MSNs-NH2 decreased from 552 cm2/g,0.74 cm3/g,2.58 nm,34 mV to 329 cm2/g,0.40 cm3/g,2.07 nm,-43 mV,. The loading rate of MSNs-NH2 on heparin was about 2% (w 鈮，
本文编号：2500709
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