使用新型的电荷切换介孔二氧化硅纳米颗粒的鳄梨种子提取物和半乳糖表面进行了修饰，以靶向抗索拉非尼的肝细胞癌
Delivery of Avocado Seed Extract Using Novel Charge-Switchable Mesoporous Silica Nanoparticles with Galactose Surface Modified to Target Sorafenib-Resistant Hepatocellular Carcinoma
影响因子:6.50000
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Aalok Basu, Arunsajee Sae-Be, Thanaphon Namporn, Orasa Suriyaphan, Pongtip Sithisarn, Jiraporn Leanpolchareanchai, Piyaporn Plommaithong, Apichat Chatsukit, Khanit Sa-Ngiamsuntorn, Parichart Naruphontjirakul, Pakatip Ruenraroengsak
摘要
索拉非尼（SR）肝细胞癌（HCC）是肝癌治疗中的一个严重问题。源自植物的许多植物化学物质表现出抗癌活性，但从未针对耐药细胞进行测试。通过浸渍分离的浸润性种子提取物（APE）的植物化学组成和抗癌活性分析了。合成了具有共轭半乳糖（GMSN）的新型设计电荷切换pH响应性纳米载体，用于递送APE，并表征了其物理化学特性。评估了药物负荷效率（％LE）和夹带效率（％EE）。对HCC（HEPG2，HUH-7）和SR-HCC（SR-HEPG2）的抗癌GMS的抗癌活性测量。APE对非耐药性HEPG2（IC50 50.9±0.83μgml-1），Huh-7（IC50 42.42.42.42.41 ec5±1ef ML-1 ec50.9±0.83μgml-1）的活动。 62.58±2.29μgml-1）细胞被确认。加载的GMSN的猿直径为131.41±14.41 nm，LE为41.08±2.09％，EE为44.96±2.26％。半乳糖功能化（55％）不会扰动原始的介孔结构。 GMSN赋予酸性培养基pH 5.5的10.3±0.61mV的正面电荷，并在2小时内快速释放APE 45％。 GMSN增强了HEPG2和SR-HEPG2细胞的细胞摄取，而胺功能化促进了其内体逃逸。在30.73±3.14（HEPG2）的非耐药性HCC和SR-HCC细胞中证明了它们的抗癌活性（HEPG2），21.86±0.83（HUH-7），35.64±1.34（sr-Hepg2）μgml-1分别与对照组合的APE，分别为APE，分别为APE。 HCC和SR-HCC以及在体内调查进一步保证。
Abstract
Sorafenib-resistant (SR) hepatocellular carcinoma (HCC) is a current serious problem in liver cancer treatment. Numerous phytochemicals derived from plants exhibit anticancer activity but have never been tested against drug-resistant cells.Avocado seed extract (APE) isolated by maceration was analysed for its phytochemical composition and anticancer activity. Novel design charge-switchable pH-responsive nanocarriers of aminated mesoporous silica nanoparticles with conjugated galactose (GMSN) were synthesised for delivering APE and their physicochemical properties were characterized. The drug loading efficiency (%LE) and entrapment efficiency (%EE) were evaluated. Anticancer activity of APE loaded GMSN was measured against HCC (HepG2, Huh-7) and SR-HCC (SR-HepG2).Anticancer activity of APE against non-resistant HepG2 (IC50 50.9 ± 0.83 μg mL-1), Huh-7 (IC50 42.41 ± 1.88 μg mL-1), and SR-HepG2 (IC50 62.58 ± 2.29 μg mL-1) cells was confirmed. The APE loaded GMSN had a diameter of 131.41 ± 14.41 nm with 41.08 ± 2.09%LE and 44.96 ± 2.26%EE. Galactose functionalization (55%) did not perturb the original mesoporous structure. The GMSN imparted positive surface charges, 10.3 ± 0.61mV at acidic medium pH 5.5 along with rapid release of APE 45% in 2 h. The GMSN boosted cellular uptake by HepG2 and SR-HepG2 cells, whereas the amine functionalized facilitated their endosomal escape. Their anticancer activity was demonstrated in non-resistant HCC and SR-HCC cells with IC50 values at 30.73 ± 3.14 (HepG2), 21.86 ± 0.83 (Huh-7), 35.64 ± 1.34 (SR-HepG2) μg mL-1, respectively, in comparison to the control and non-encapsulated APE.APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further in vivo investigation.