Carbon Nanomaterials for Theranostic Systems

MasterCarbon nanomaterials have been widely investigated for various biomedical applications. For example, single walled carbon nanotubes (SWNTs) and graphenes have been integrated into FET biosensors, and the luminescence from SWNTs and graphene oxides has been exploited for bioimaging applications. Recently, fluorescent carbon dots (Cdots) have attracted many researchers due to their chemical inertness, excellent water solubility, and unique optical properties. In this work, fluorescent Cdots were synthesized and applied to the bioimaging for target specific delivery of hyaluronic acid (HA) derivatives. In addition, we synthesized 3,4-dihydroxy-L-phenylalanine conjugated HA (HA-DOPA) encapsulating Cdots and epirubicin for theranostic applications. The photothermal effect of Cdots was compared with those of graphene and graphene oxide. Chapter 1 describes the introduction to carbon nanomaterials in terms of their photoluminescence and photothermal characteristics. Then, HA was introduced focusing on the biological functions and unique physico-chemical properties. Chapter 2 describes the synthesis and characterization of water soluble Cdots and HA-Cdot conjugate, and their bioimaging applications. PEG diamine capped Cdots were synthesized by the pyrolysis of citric acid in a hot solvent. The prepared Cdots showed strong fluorescence under UV excitation with excitation wavelength dependent emission properties. The morphology of Cdots was mostly spherical with a size of 4-6 nm. HRTEM revealed that the core of Cdots was crystalline with a lattice spacing of 0.25 nm, which was very close to (100) facet of graphite. HA-Cdot conjugate was synthesized by amide bond formation between amine groups of Cdot and carboxylic groups of HA. 1H NMR analysis confirmed the successful synthesis of HA-Cdot conjugate. The MTS cytotoxicity tests confirmed the negligible cytotoxicity of Cdots and HA-Cdot conjugate. The prepared HA-Cdot conjugates were applied to the bioimaging for target specific intracellular delivery of HA by the HA receptor mediated endocytosis. The competitive cellular uptake tests to HEK293 cells without HA receptors and B16F1 cells with HA receptors confirmed the target specific cellular uptake of HA-Cdot conjugates by the HA receptor mediated endocytosis. On the basis of the in vitro bioimaging, in vivo bioimaging of Cdots and HA-Cdot conjugate was also carried out, which revealed the target specific delivery of HA-Cdot conjugate to the liver with HA receptors such as HARE and CD44. Chapter 3 describes HA-DOPA/Cdot complex encapsulating epirubicin for theranostic applications. Oil soluble Cdots were synthesized using the same protocol for water soluble Cdots except the capping agent of 1-hexadecylamine and the solvent of 1-octadecene. Oil soluble Cdots also showed strong fluorescence under UV excitation. TEM analysis revealed the spherical morphology of Cdots with a size of 6-8 nm. HA-DOPA conjugate was successfully synthesized by the amide bond formation using the EDC chemistry, which was confirmed by 1H NMR analysis. The complex formation between HA-DOPA and oil soluble Cdots was performed in the presence of epirubicin by ultrasonication. Then, in vitro anti-tumor activity of HA-DOPA/epirubicin/Cdot complex was confirmed by the MTT test. Chapter 4 describes the applications of carbon materials to photothermal therapy. Laser irradiation onto Cdots, HA-Cdot conjugate, and nanographene oxide resulted in the time and concentration dependent temperature increase, which reflected the possibility of carbon materials for photothermal therapy. Taken together, we could confirm the feasibility of carbon materials for various bioimaging and theranostic applications