利用新型带有半乳糖表面修饰的电荷可切换多孔硅纳米粒子靶向耐索拉非尼肝细胞癌的芒果籽提取物递送
Delivery of Avocado Seed Extract Using Novel Charge-Switchable Mesoporous Silica Nanoparticles with Galactose Surface Modified to Target Sorafenib-Resistant Hepatocellular Carcinoma
DOI 原文链接
用sci-hub下载
如无法下载，请从 Sci-Hub 选择可用站点尝试。
影响因子:6.5
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
DOI:
10.2147/IJN.S478574
摘要
索拉非尼耐药（SR）肝细胞癌（HCC）是当前肝癌治疗中的一大难题。许多源自植物的植物化学物质表现出抗癌活性，但尚未在耐药细胞中进行测试。通过浸泡法分离的芒果籽提取物（APE）被分析其植物化学成分和抗癌活性。合成了新型带有半乳糖连接的电荷可切换pH响应型纳米载体——氨基化多孔硅纳米粒子（GMSN），用于递送APE，并对其理化性质进行了表征。评估了药物负载效率（%LE）和包封效率（%EE）。检测了APE负载GMSN的抗癌活性，作用于HCC（HepG2、Huh-7）及SR-HCC（SR-HepG2）细胞。结果证实了APE对非耐药HepG2（IC50 50.9 ± 0.83 μg/mL）、Huh-7（IC50 42.41 ± 1.88 μg/mL）和SR-HepG2（IC50 62.58 ± 2.29 μg/mL）细胞的抗癌作用。负载APE的GMSN直径为131.41 ± 14.41 nm，具有41.08 ± 2.09%的负载率（LE）和44.96 ± 2.26%的包封效率（EE）。半乳糖功能化（55%）未破坏其原有的多孔结构。GMSN赋予正表面电荷，在酸性介质pH 5.5下电荷为10.3 ± 0.61 mV，并在2小时内迅速释放APE（45%）。GMSN增强了HepG2和SR-HepG2细胞的细胞摄取，而氨基功能化则促进了它们的内体逃逸。其抗癌效果在非耐药HCC和SR-HCC细胞中表现出IC50值分别为30.73 ± 3.14（HepG2）、21.86 ± 0.83（Huh-7）和35.64 ± 1.34（SR-HepG2）μg/mL，相较于对照组和未包封的APE具有更佳的活性。负载APE的GMSN在非耐药HCC和SR-HCC中均表现出高效的抗癌效果，值得进一步进行体内研究。
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.