【摘要】：本文基于聚酰胺-胺[poly(amido amine),PAMAM G5]樹狀大分子,通過化學(xué)合成葉酸(folic acid,FA)介導(dǎo)的、冰片(borneol,BO)修飾的新型納米載體(FA-BO-PAMAM),并包載抗癌藥物阿霉素(doxorubicin,DOX),以達(dá)到增加藥物血腦屏障(blood-brain barrier,BBB)的透過性和提高腦膠質(zhì)瘤靶向性的目的。通過1H NMR驗(yàn)證合成載體的結(jié)構(gòu),采用透射電鏡(TEM)和納米粒度-電位分析儀(DLS)分別對FA-BO-PAMAM的形貌、粒徑和表面電勢進(jìn)行表征;另外基于腦血管內(nèi)皮細(xì)胞(HBMEC)和腦膠質(zhì)瘤細(xì)胞(C6)雙細(xì)胞模型考察載體的細(xì)胞毒性,以及載藥復(fù)合物體外跨BBB膜轉(zhuǎn)運(yùn)的能力、細(xì)胞攝取效率和體外抗腫瘤的效果。1H NMR的結(jié)果表明FA-BO-PAMAM合成成功,在TEM下呈類圓形,大小分布均勻,粒徑為(22.28±0.42)nm,zeta電位為(7.6±0.89)m V(n=3)。細(xì)胞毒性和體外跨BBB轉(zhuǎn)運(yùn)實(shí)驗(yàn)結(jié)果顯示,PAMAM功能化修飾冰片顯著地降低了PAMAM毒性,提高了生物安全性,同時(shí)增加了載藥復(fù)合物跨BBB轉(zhuǎn)運(yùn)率。細(xì)胞攝取和體外抗腫瘤實(shí)驗(yàn)結(jié)果表明,葉酸的修飾增加了C6細(xì)胞對載藥復(fù)合物的總攝取量,且提高了體外對C6細(xì)胞的抑制率。因此,該新型靶向納米載體增加了藥物在腫瘤部位的蓄積量,顯示了其在治療腦膠質(zhì)瘤應(yīng)用中的潛能。
[Abstract]:Based on the dendritic macromolecules of poly (amido amine) (poly (amido amine) PamAM-G5, folic acid (folic acid,FA) -mediated synthesis was carried out in this paper. Borneol (borneol,BO) modified novel nano-carrier (FA-BO-PAMAM) was coated with adriamycin (doxorubicin,DOX) to enhance the permeability of blood-brain barrier (blood-brain barrier,BBB) and the targeting of glioma. The structure of the synthesized support was verified by 1H NMR. The morphology, particle size and surface potential of FA-BO-PAMAM were characterized by transmission electron microscope (TEM) (TEM) and nanocrystalline grain-potential analyzer (DLS). In addition, the cytotoxicity of the vector and the ability of the drug carrier complex to transport through the BBB membrane in vitro were investigated based on the dual cell models of (HBMEC) and C6 cells of cerebrovascular endothelial cells. The results of cell uptake efficiency and in vitro anti-tumor effect. 1H NMR showed that FA-BO-PAMAM was synthesized successfully. The FA-BO-PAMAM was round and uniform in size and size under TEM, and its particle size was (22.28 鹵0.42) nm,zeta potential was (7.6 鹵0.89) m V (nm3). The results of cytotoxicity and in vitro translocation of BBB showed that Pam functionalized borneol significantly decreased the toxicity of PAMAM, improved the biosafety and increased the translocation rate of BBB. The results of cell uptake and in vitro antitumor experiments showed that folic acid modification increased the total uptake of C6 cells and the inhibition rate of C6 cells in vitro. Therefore, the novel targeted nanoparticles increase the accumulation of drugs in tumor sites and show their potential in the treatment of glioma.
【作者單位】： 浙江中醫(yī)藥大學(xué)藥學(xué)院;
【基金】：國家自然科學(xué)基金資助項(xiàng)目(81274089,81473361) 浙江省自然科學(xué)基金資助項(xiàng)目(LZ13H280001,LY12H280004) 浙江省科技創(chuàng)新團(tuán)隊(duì)資助項(xiàng)目(2010R500445)
【分類號】：R943

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本文編號：2234409