Ocsoy Ismail, Isiklan Nuran, Cansiz Sena, Özdemir Nalan, Tan Weihong
Center for Research at the Bio/Nano Interface, Department of Chemistry and Shands Cancer Center, UF Genetics Institute and McKnight Brain Institute, University of Florida, Gainesville, Florida, 32611; Department of Analytical Chemistry, Faculty of Pharmacy, Erciyes University, Kayseri, 38039 Turkey; Nanotechnology Research Center (ERNAM), Erciyes University, Kayseri, 38039 Turkey.
Department of Chemistry, Science and Arts Faculty, Kırıkkale University, Kırıkkale, 7100 Turkey.
RSC Adv. 2016;6(36):30285-30292. doi: 10.1039/C6RA06798K. Epub 2016 Mar 18.
Aptamer-functionalized magnetic graphene oxide conjugates loaded with indocyanine green (ICG) dye, or Apt@ICG@mGO, have been successfully developed for dual-targeted photothermal and photodynamic therapy. In general, a drug or its carrier or their dosage can be imprtant important issues in terms of toxicity. However, in this system, each component used is quite safe, biocompatibe and clean. For instance, ICG, a Food and Drug Administration (FDA) approved near-infrared (NIR) dye, serves as both a photothermal and photodynamic agent. It is immobilized on the surface of mGO via a physical interaction called "π-π stacking". The mGO, as a most biocomptible member of the carbo family, is selected for use as a platform for aptamer and ICG dye conjugation, as well as as a photothermal agent. The light in the near-infrared region (NIR) was chosen as a harmless light source for activating the agents for photothermal therapy (PTT) and photodynamic therapy (PDT). The magnetic properties of mGO are also used for separation of Apt@ICG@mGO conjugates from the reaction medium. Aptamer sgc8 acts as a targeting ligand to selectively and specifically bind to a protein on the membrane of cancer cell line CCRF-CEM. After the aptamer- functionalized ICG@mGO conjugates are incubated with target CEM cells at 37 °C for 2 hours, they are bound to cells or they may be internalized into the cell via endocytosis. More significantly, we demonstrated that the Apt@ICG@mGO conjugates produce heat for photothermal therapy (PTT) and singlet oxygen for photodynamic therapy (PDT) upon NIR laser irradiation at 808 nm. Thus, remarkably efficient cancer cell destructions with 41% and 60% and 82% cell killing using 10, 50 and 100 ppm Apt@ICG@mGO, respectively are achieved in 5 min light exposure.
负载吲哚菁绿（ICG）染料的适体功能化磁性氧化石墨烯共轭物，即Apt@ICG@mGO，已成功用于双靶点光热和光动力治疗。一般来说，就毒性而言，药物、其载体或它们的剂量可能是重要问题。然而，在该系统中，所使用的每种成分都相当安全、具有生物相容性且纯净。例如，ICG是一种经美国食品药品监督管理局（FDA）批准的近红外（NIR）染料，既是光热剂又是光动力剂。它通过一种称为“π-π堆积”的物理相互作用固定在mGO表面。mGO作为碳家族中最具生物相容性的成员，被选作用于适体与ICG染料共轭的平台，以及用作光热剂。近红外区域（NIR）的光被选作激活用于光热治疗（PTT）和光动力治疗（PDT）的试剂的无害光源。mGO的磁性也用于从反应介质中分离Apt@ICG@mGO共轭物。适体sgc8作为靶向配体，选择性且特异性地结合癌细胞系CCRF-CEM膜上的一种蛋白质。在37℃下将适体功能化的ICG@mGO共轭物与靶CEM细胞孵育2小时后，它们会与细胞结合，或者可能通过内吞作用进入细胞。更重要的是，我们证明了在808nm近红外激光照射下，Apt@ICG@mGO共轭物会产生用于光热治疗（PTT）的热量和用于光动力治疗（PDT）的单线态氧。因此，在5分钟的光照下，分别使用10、50和100ppm的Apt@ICG@mGO可实现显著高效的癌细胞破坏，细胞杀伤率分别为41%、60%和82%。
