Epigallocatechin Gallate-Gold Nanoparticles Exhibit Superior Antitumor Activity Compared to Conventional Gold Nanoparticles: Potential Synergistic Interactions
Epigallocatechin Gallate-Gold Nanoparticles Exhibit Superior Antitumor Activity Compared to Conventional Gold Nanoparticles: Potential Synergistic Interactions
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DOI：
10.3390/nano9030396
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发表时间：
2019-03-08
期刊：
影响因子：
5.3
通讯作者：
Singh, Seema
中科院分区：
文献类型：
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作者：
Chavva, Suhash Reddy;Deshmukh, Sachin Kumar;Singh, Seema
表没食子儿茶素没食子酸酯（EGCG）具有显著的抗肿瘤活性，并以高亲和力结合癌细胞上过表达的层粘连蛋白受体。金纳米粒子（GNP）作为优良的药物载体，并保护结合药物免受酶代谢。采用还原法制备了柠檬酸-金纳米粒子（C-GNP）和EGCG-金纳米粒子（E-GNP），并用紫外-可见光谱、透射电子显微镜（TEM）和动态光散射（DLS）对其进行了表征。通过水溶性四唑盐（WST-1）测定评估柠檬酸盐、EGCG、C-GNP和E-GNP的细胞毒性。通过TEM和原子吸收光谱法（AAS）进行纳米颗粒细胞摄取研究。采用透析法评价药物释放。细胞活力研究显示，与EGCG或C-GNP相比，E-GNP具有更大的生长抑制作用。细胞摄取研究表明，与C-GNP不同，E-GNP被癌细胞比非癌细胞更有效地摄取。我们发现E-GNP纳米制剂以持续的方式释放EGCG。此外，数据显示，与EGCG和C-GNP相比，E-GNP在癌细胞中诱导更多的凋亡。从机制的角度来看，我们观察到，E-GNP抑制核转位和核因子-κ B（NF-κ B）的转录活性的效力大于EGCG，而C-GNP只有最低限度的有效性。总之，我们的数据表明，E-GNP可以作为有效的肿瘤选择性化学毒性剂。
Epigallocatechin gallate (EGCG) possesses significant antitumor activity and binds to laminin receptors, overexpressed on cancer cells, with high affinity. Gold nanoparticles (GNPs) serve as excellent drug carriers and protect the conjugated drug from enzymatic metabolization. Citrate-gold nanoparticles (C-GNPs) and EGCG-gold nanoparticles (E-GNPs) were synthesized by reduction methods and characterized with UV-visible spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Cytotoxicity of citrate, EGCG, C-GNPs, and E-GNPs was evaluated by the water-soluble tetrazolium salt (WST-1) assay. Nanoparticle cellular uptake studies were performed by TEM and atomic absorption spectroscopy (AAS). Dialysis method was employed to assess drug release. Cell viability studies showed greater growth inhibition by E-GNPs compared to EGCG or C-GNPs. Cellular uptake studies revealed that, unlike C-GNPs, E-GNPs were taken up more efficiently by cancerous cells than noncancerous cells. We found that E-GNP nanoformulation releases EGCG in a sustained fashion. Furthermore, data showed that E-GNPs induced more apoptosis in cancer cells compared to EGCG and C-GNPs. From the mechanistic standpoint, we observed that E-GNPs inhibited the nuclear translocation and transcriptional activity of nuclear factor-kappaB (NF-kappa B) with greater potency than EGCG, whereas C-GNPs were only minimally effective. Altogether, our data suggest that E-GNPs can serve as potent tumor-selective chemotoxic agents.