Size Dependency of Selective Cellular Uptake of Epigallocatechin Gallate-modified Gold Nanoparticles for Effective Radiosensitization
Size Dependency of Selective Cellular Uptake of Epigallocatechin Gallate-modified Gold Nanoparticles for Effective Radiosensitization
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DOI：
10.1021/acsabm.1c01149
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发表时间：
2021-12-24
影响因子：
4.7
通讯作者：
Ooya, Tooru
中科院分区：
文献类型：
--
作者：
Gan, Ning;Wakayama, Chihiro;Ooya, Tooru
癌症的高发病率和死亡率使其成为一个全球性的健康问题。然而，传统的癌症治疗有一些缺点，特别是由于对癌细胞的选择性毒性低，副作用严重。金纳米颗粒（AuNPs）是一种优良的药物载体，可提高药物的传递效率，在光热和放射治疗中具有广阔的应用前景。（-）-表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中主要的多酚类抗氧化成分，具有有效的抗肿瘤作用，并特异性结合67 kDa层粘连蛋白受体，该受体在几种癌细胞系如HeLa和MDA-MB-231细胞表面过表达。我们以n(EGCG)/n（金）为1:2 ~ 10:1的比例合成了EGCG修饰的AuNPs (EGCG-AuNPs)，并与以柠檬酸盐为还原剂制备的传统AuNPs（柠檬酸盐-AuNPs）进行了尺寸、形态、稳定性、抗氧化能力、细胞毒性、细胞摄取和体外摄取机制的比较。在HeLa细胞中，EGCG-AuNPs(10:1)（直径135 nm，海胆样形状）表现出最高的细胞摄取。相反，EGCG-AuNPs(1:2)（直径39 nm，球形）优先被MDA-MB-231细胞吸收。正常细胞（NIH3T3细胞）对EGCG-AuNPs的细胞摄取是一种非特异性的方式，并且摄取量受到抑制。在MDA-MB-231细胞摄取EGCG-AuNPs（1:2）后，x射线照射可显著增强照射诱导的细胞死亡。这些发现表明，直径为39nm的EGCG-AuNPs可以增强细胞摄取，并可能用于EGCG-AuNPs联合治疗乳腺癌。
The high incidence and mortality of cancer make it a global health issue. However, conventional cancer therapies have several disadvantages, especially serious side effects due to low selective toxicity to cancer cells. Gold nanoparticles (AuNPs) are an excellent drug carrier, enhance drug delivery efficiency, and hold promise for photothermal and radiation therapies. (-)-Epigallocatechin-3-gallate (EGCG) is the major polyphenolic antioxidant constituent of green tea, has a potent antitumor effect, and binds specifically to the 67 kDa laminin receptor, which is overexpressed on the surface of several cancer cell lines such as HeLa and MDA-MB-231 cells. We synthesized EGCG-modified AuNPs (EGCG-AuNPs) using ratios (n(EGCG)/n(gold)) from 1:2 to 10:1 and evaluated their size, morphology, stability, antioxidant ability, cytotoxicity, cellular uptake, and uptake mechanisms in vitro in comparison with the conventional AuNPs prepared by using citrate as the reducing agent (citrate-AuNPs). In HeLa cells, EGCG-AuNPs (10:1) (135 nm diameter, sea-urchin-like shape) exhibited the highest cellular uptake. Conversely, EGCG-AuNPs (1:2) (39 nm diameter, spherical shape) were preferentially taken up by MDA-MB-231 cells. Cellular uptake of EGCG-AuNPs toward normal cells (NIH3T3 cells) was found to be in a nonspecific manner, and the amount of uptake was suppressed. X-ray irradiation after cellular uptake of EGCG-AuNPs (1:2) in MDA-MB-231 cells significantly enhanced irradiation-induced cell death. These findings suggest enhanced cellular uptake of EGCG-AuNPs with a 39 nm diameter and their potential use in combinatorial therapeutics of EGCG-AuNPs for breast cancer.