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新型电荷可转换介孔硅纳米粒子递送鳄梨仁提取物，并用半乳糖表面修饰以靶向索拉非尼耐药肝癌。

Delivery of Avocado Seed Extract Using Novel Charge-Switchable Mesoporous Silica Nanoparticles with Galactose Surface Modified to Target Sorafenib-Resistant Hepatocellular Carcinoma.

机构信息

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

Department of Food Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.

出版信息

Int J Nanomedicine. 2024 Oct 14;19:10341-10365. doi: 10.2147/IJN.S478574. eCollection 2024.

DOI:10.2147/IJN.S478574
PMID:39430309
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11488512/
Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

Anticancer activity of APE against non-resistant HepG2 (IC 50.9 ± 0.83 μg mL), Huh-7 (IC 42.41 ± 1.88 μg mL), and SR-HepG2 (IC 62.58 ± 2.29 μg mL) 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 IC values at 30.73 ± 3.14 (HepG2), 21.86 ± 0.83 (Huh-7), 35.64 ± 1.34 (SR-HepG2) μg mL, respectively, in comparison to the control and non-encapsulated APE.

CONCLUSION

APE loaded GMSN is highly effective against both non-resistant HCC and SR-HCC and warrants further investigation.

摘要

背景

索拉非尼耐药（SR）肝细胞癌（HCC）是肝癌治疗中的一个严重问题。许多来源于植物的植物化学物质具有抗癌活性，但从未在耐药细胞中进行过测试。

方法

通过浸渍法分离鳄梨籽提取物（APE），分析其植物化学成分和抗癌活性。设计了新型电荷可转换 pH 响应型氨基功能化介孔硅纳米载体，用于载运 APE，并对其理化性质进行了表征。评价了载药效率（%LE）和包封效率（%EE）。测定了负载 APE 的 GMSN 对 HCC（HepG2、Huh-7）和 SR-HCC（SR-HepG2）的抗癌活性。

结果

证实了 APE 对非耐药 HepG2（IC 50.9 ± 0.83 μg mL）、Huh-7（IC 42.41 ± 1.88 μg mL）和 SR-HepG2（IC 62.58 ± 2.29 μg mL）细胞的抗癌活性。负载 APE 的 GMSN 直径为 131.41 ± 14.41nm，载药效率为 41.08 ± 2.09%，包封效率为 44.96 ± 2.26%。半乳糖功能化（55%）并没有破坏原始的介孔结构。GMSN 赋予了正表面电荷，在酸性介质 pH 5.5 下为 10.3 ± 0.61mV，同时在 2 小时内快速释放 45%的 APE。GMSN 促进了 HepG2 和 SR-HepG2 细胞的细胞摄取，而伯胺官能化促进了它们的内体逃逸。它们在非耐药 HCC 和 SR-HCC 细胞中的抗癌活性与对照组和非包封 APE 相比，IC 值分别为 30.73 ± 3.14（HepG2）、21.86 ± 0.83（Huh-7）和 35.64 ± 1.34（SR-HepG2）μg mL。

结论

负载 APE 的 GMSN 对非耐药 HCC 和 SR-HCC 均具有高度疗效，值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/591d/11488512/b58f69d0fe9d/IJN-19-10341-g0010.jpg
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