【摘要】：在過去的20年里,納米技術(shù)經(jīng)歷了快速的發(fā)展。由于介孔硅納米粒子(MSNs)具有良好的物理-化學(xué)特性和生物相容性,因此它們?cè)粡V泛應(yīng)用于藥物傳遞、藥物靶向、基因轉(zhuǎn)染和細(xì)胞追蹤等各個(gè)方面。在過去的幾十年里盡管基于功能化的MSNs的藥物傳遞系統(tǒng)(DDSs)的體外研究取得了良好的結(jié)果,但有關(guān)這些功能化的以MSNs為基礎(chǔ)的DDSs的生物安全性和治療效果的體內(nèi)評(píng)價(jià)近年來才剛剛開始。本文通過以下步驟進(jìn)行研究:(1)首先,我們用溶膠-凝膠法合成了球形、粒徑為120-160 nm、無序的介孔結(jié)構(gòu)、分散性較好的氨基化介孔硅納米粒子(MSNs-NH2);(2)其次,將功能性活性分子肝素共價(jià)結(jié)合在MSNs-NH2上形成肝素化介孔硅納米粒子(MSNs-HP)。結(jié)果表明肝素在MSNs-NH2上的固定對(duì)其形態(tài)學(xué)并無影響,但MSNs-NH2的BET表面積、孔容、孔徑和Zeta電位分別從552 cm2/g,0.74 cm3/g,2.58 nm,34 mV減少至329 cm2/g,0.40 cm3/g,2.07 nm,-43 mV,用甲苯胺藍(lán)法測(cè)定MSNs-NH2對(duì)肝素的負(fù)載率約為2%(w/w);(3)然后,我們通過物理吸附法將阿霉素(DOX)負(fù)載到MSNs-HP上,并對(duì)DOX進(jìn)行定量分析測(cè)得MSNs-HP對(duì)DOX的負(fù)載率為4%(w/w)。根據(jù)其體內(nèi)和體外釋放曲線,可以看出在起初的8 h內(nèi)DOX出現(xiàn)突釋,整個(gè)釋放過程超過了70 h。將負(fù)載DOX的納米粒子靜脈注射后,DOX在血漿中的峰濃度可以維持6 h。結(jié)果表明MSNs-HP可以穿透進(jìn)入癌細(xì)胞并且延緩抗癌藥物DOX的釋放,這有助于提高治療效果。最后我們以H22移植鼠為動(dòng)物實(shí)驗(yàn)?zāi)Ｐ蛯?duì)所合成的納米粒子進(jìn)行了體內(nèi)評(píng)價(jià),結(jié)果顯示MSNs-HP在負(fù)載較少量藥物的情況下就能與單獨(dú)使用較大劑量的抗腫瘤藥物產(chǎn)生類似的效果。負(fù)載DOX的MSNs-HP的腫瘤抑制率(58%)遠(yuǎn)遠(yuǎn)超過了在納米粒子中的DOX的腫瘤抑制率(18%),并且與其大劑量(7倍劑量)的DOX的抑制率(67%)相近,這表明MSNs-HP的使用可以顯著提高DOX的抗腫瘤效果。此外,我們發(fā)現(xiàn)這個(gè)系統(tǒng)比使用較大劑量的藥物更加安全。這些因素可能會(huì)使MSNs-HP成為抗腫瘤藥物傳遞的一種高效、低毒的載體。
[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，

本文編號(hào)：2500709