Maji Swarup Kumar, Mandal Amal Kumar, Nguyen Kim Truc, Borah Parijat, Zhao Yanli
†Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.
‡School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, 639798, Singapore.
ACS Appl Mater Interfaces. 2015 May 13;7(18):9807-16. doi: 10.1021/acsami.5b01758. Epub 2015 May 4.
Development of efficient artificial enzymes is an emerging field in nanobiotechnology, since these artificial enzymes could overcome serious disadvantages of natural enzymes. In this work, a new nanostructured hybrid was developed as a mimetic enzyme for in vitro detection and therapeutic treatment of cancer cells. The hybrid (GSF@AuNPs) was prepared by the immobilization of gold nanoparticles (AuNPs) on mesoporous silica-coated nanosized reduced graphene oxide conjugated with folic acid, a cancer cell-targeting ligand. The GSF@AuNPs hybrid showed unprecedented peroxidase-like activity, monitored by catalytic oxidation of a typical peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), in the presence of H2O2. On basis of this peroxidase activity, the hybrid was utilized as a selective, quantitative, and fast colorimetric detection probe for cancer cells. Finally, the hybrid as a mimetic enzyme was employed for H2O2- and ascorbic acid (AA)-mediated therapeutics of cancer cells. In vitro experiments using human cervical cancer cells (HeLa cells) exhibited the formation of reactive oxygen species (OH(•) radical) in the presence of peroxidase-mimic GSF@AuNPs with either exogenous H2O2 or endogenous H2O2 generated from AA, leading to an enhanced cytotoxicity to HeLa cells. In the case of normal cells (human embryonic kidney HEK 293 cells), the treatment with the hybrid and H2O2 or AA showed no obvious damage, proving selective killing effect of the hybrid to cancer cells.
高效人工酶的开发是纳米生物技术中一个新兴的领域，因为这些人工酶能够克服天然酶的严重缺点。在这项工作中，一种新型的纳米结构杂化物被开发出来，作为一种模拟酶用于癌细胞的体外检测和治疗。这种杂化物（GSF@AuNPs）是通过将金纳米颗粒（AuNPs）固定在与叶酸（一种癌细胞靶向配体）共轭的介孔二氧化硅包覆的纳米尺寸还原氧化石墨烯上制备而成。GSF@AuNPs杂化物表现出前所未有的过氧化物酶样活性，通过在H2O2存在下催化氧化典型的过氧化物酶底物3,3',5,5'-四甲基联苯胺（TMB）进行监测。基于这种过氧化物酶活性，该杂化物被用作癌细胞的选择性、定量和快速比色检测探针。最后，该杂化物作为模拟酶用于H2O2和抗坏血酸（AA）介导的癌细胞治疗。使用人宫颈癌细胞（HeLa细胞）进行的体外实验表明，在存在过氧化物酶模拟物GSF@AuNPs的情况下，无论是外源性H2O2还是由AA产生的内源性H2O2，都会产生活性氧（OH(•)自由基），从而增强对HeLa细胞的细胞毒性。对于正常细胞（人胚胎肾HEK 293细胞），用该杂化物与H2O2或AA处理未显示明显损伤，证明了该杂化物对癌细胞的选择性杀伤作用。
