Khandelwal Puneet, Alam Aftab, Choksi Arpankumar, Chattopadhyay Samit, Poddar Pankaj
Physical & Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune 411008, India.
National Center for Cell Science, Ganeshkhind, Pune 411 007, India.
ACS Omega. 2018 May 31;3(5):4776-4785. doi: 10.1021/acsomega.8b00113. Epub 2018 May 1.
Gold nanoparticles (Au NPs) have been thoroughly investigated for anti-cancer therapy. However, their undesired high gold content remains a problem when injected into the body for drug delivery applications. In this report, we made an effort to conjugate the curcumin molecules on the surface of gold quantum clusters (Au QCs) by a novel in situ synthesis method which provides an alternative route to not only reduce the metallic content but also increase the water solubility of curcumin and the loading efficiency. Here, curcumin itself acts as a reducing and capping agent for the synthesis of Au QCs. The UV-vis absorption, fluorescence, transmission electron microscopy, and electrospray ionization mass spectrometry results confirmed the synthesis of fluorescent Au QCs. Curcumin-conjugated Au NPs (C-Au NPs) and glutathione (GSH)-conjugated Au QCs (GSH-Au QCs) were also synthesized to visualize the effect of particle size and the capping agent, respectively, on the cytotoxicity to normal and cancer cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the curcumin-conjugated Au QCs (C-Au QCs) were less cytotoxic to normal cells while almost the same cytotoxic to cancer cells in comparison to curcumin itself, which indicates that curcumin preserves its anticancer property even after binding to the Au QCs. However, C-Au NPs and GSH-Au QCs did not show any cytotoxicity against the normal and cancer cells at the concentration used. The western blot assay indicated that C-Au QCs promote apoptosis in cancer cells. Further, the in vivo study on severe combined immunodeficiency mice showed that C-Au QCs also inhibited the tumor growth efficiently without showing significant toxicity to internal organs.
金纳米颗粒（Au NPs）已被深入研究用于抗癌治疗。然而，当将其注射到体内用于药物递送应用时，其不期望的高金含量仍然是一个问题。在本报告中，我们努力通过一种新颖的原位合成方法将姜黄素分子缀合在金量子簇（Au QCs）的表面，该方法不仅提供了一种降低金属含量的替代途径，还提高了姜黄素的水溶性和负载效率。在此，姜黄素本身充当合成Au QCs的还原剂和封端剂。紫外可见吸收、荧光、透射电子显微镜和电喷雾电离质谱结果证实了荧光Au QCs的合成。还合成了姜黄素缀合的Au NPs（C-Au NPs）和谷胱甘肽（GSH）缀合的Au QCs（GSH-Au QCs），以分别观察粒径和封端剂对正常细胞和癌细胞细胞毒性的影响。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐测定表明，与姜黄素本身相比，姜黄素缀合的Au QCs（C-Au QCs）对正常细胞的细胞毒性较小，而对癌细胞的细胞毒性几乎相同，这表明姜黄素即使在与Au QCs结合后仍保留其抗癌特性。然而，C-Au NPs和GSH-Au QCs在所使用的浓度下对正常细胞和癌细胞均未显示出任何细胞毒性。蛋白质免疫印迹分析表明，C-Au QCs促进癌细胞凋亡。此外，对严重联合免疫缺陷小鼠的体内研究表明，C-Au QCs也能有效抑制肿瘤生长，而对内部器官未显示出明显毒性。
