索拉非尼耐药（SR）肝细胞癌（HCC）是当前肝癌治疗中的一个严重问题。许多源自植物的植物化学物质表现出抗癌活性，但从未针对耐药细胞进行过测试。分析了通过浸渍分离的鳄梨种子提取物 (APE) 的植物化学成分和抗癌活性。合成了具有共轭半乳糖（GMSN）的新型电荷可切换 pH 响应纳米载体，用于递送 APE，并对其物理化学性质进行了表征。评估载药效率（%LE）和包封效率（%EE）。测量加载 APE 的 GMSN 对 HCC (HepG2、Huh-7) 和 SR-HCC (SR-HepG2) 的抗癌活性。APE 对非耐药 HepG2 的抗癌活性 (IC50 50.9 ± 0.83 μg mL-1)、Huh-7 (IC50 42.41 ± 1.88 μg mL-1) 和 SR-HepG2 (IC50 62.58 ± 2.29 μg mL-1) 细胞得到确认。加载 APE 的 GMSN 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%）不会扰乱原始的介孔结构。 GMSN 在酸性介质 pH 5.5 下赋予表面正电荷 10.3 ± 0.61mV，并在 2 小时内快速释放 45% 的 APE。 GMSN 增强了 HepG2 和 SR-HepG2 细胞的细胞摄取，而胺功能化则促进了它们的内体逃逸。它们的抗癌活性在非耐药 HCC 和 SR-HCC 细胞中得到证实，IC50 值分别为 30.73 ± 3.14 (HepG2)、21.86 ± 0.83 (Huh-7)、35.64 ± 1.34 (SR-HepG2) μg mL-1，与对照和非封装 APE 相比。负载 APE 的 GMSN 对非耐药性 HCC 和 SR-HCC 均非常有效，值得进一步的体内研究。© 2024 Basu 等人。

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.© 2024 Basu et al.