Cancer cells inhibition by cationic carbon dots targeting the cellular nucleus
Cancer cells inhibition by cationic carbon dots targeting the cellular nucleus
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DOI：
10.1016/j.jcis.2023.01.086
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发表时间：
2023-01-24
影响因子：
9.9
通讯作者：
Leblanc, Roger M.
中科院分区：
文献类型：
--
作者：
Chen, Jiuyan;Li, Fang;Leblanc, Roger M.
细胞核靶向在癌症治疗中非常重要。阳离子碳量子点（CCDs）是一种潜在的纳米粒子，可以进入细胞并穿透核膜。虽然一些CCD已被研究用于核靶向并应用于核成像，但来自药物的CCD，能够靶向细胞核，与DNA结合并抑制癌细胞生长的还没有报道。本课题以1，2，4，5-苯四胺（Y15，一种黏着斑激酶抑制剂）、叶酸和1，2-乙二胺为前驱体，通过水热法制备了Y15-CD。基于结构、光学和形貌表征，Y15-CD具有丰富的胺基和氮结构，激发依赖的光致发光发射，以及2 ~ 4 nm的小粒径。通过琼脂糖凝胶电泳、紫外-可见吸收光谱、荧光发射光谱和圆二色谱等方法对Y15-CD与DNA的结合进行了研究，结果表明Y15-CD与DNA的结合可能是以静电相互作用和部分嵌入的方式进行的。此外，在人包皮成纤维细胞（HFF）、前列腺癌（PC 3）和骨肉瘤细胞（U2 OS）中的细胞成像和细胞毒性研究表明Y15-CD的核靶向和抗癌能力。最有趣的是，Y15-CD对癌细胞（PC 3和U2 OS）比对正常细胞（HFF）表现出更高的细胞毒性，推断Y15-CD可能潜在地应用于癌症治疗。(c)2023爱思唯尔公司All rights reserved.
Nucleus targeting is tremendously important in cancer therapy. Cationic carbon dots (CCDs) are potential nanoparticles which might enter cells and penetrate nuclear membranes. Although some CCDs have been investigated in nucleus targeting and applied in nuclear imaging, the CCDs derived from drugs, that are able to target the nucleus, bind with DNA and inhibit the growth of cancer cells have not been reported. In this project, 1, 2, 4, 5-benzenetetramine (Y15, a focal adhesion kinase inhibitor) derived cationic carbon dots (Y15-CDs) were prepared via a hydrothermal approach utilizing Y15, folic acid and 1,2-ethylenediamine as precursors. Based on the structural, optical, and morphologic characterizations, Y15-CDs possess rich amine groups and nitrogen in structure, an excitation-dependent photolumines-cence emission, and a small particle size of 2 to 4 nm. The DNA binding experiments conducted through agarose gel electrophoresis, UV-vis absorption, fluorescence emission, and circular dichroism spectro-scopies, prove that Y15-CDs might bind with DNA via electrostatic interactions and partially intercalative binding modes. In addition, the cell imaging and cytotoxicity studies in human foreskin fibroblasts (HFF), prostate cancer (PC3) and osteosarcoma cells (U2OS) indicate the nucleus targeting and anticancer abilities of Y15-CDs. Most interestingly, Y15-CDs exhibit a higher cytotoxicity to cancer cells (PC3 and U2OS) than to normal cells (HFF), inferring that Y15-CDs might be potentially applied in cancer therapy.(c) 2023 Elsevier Inc. All rights reserved.