Hyaluronate Modified Bimetallic Nanomaterials for Biomedical Applications

Abstract

Recently, bimetallic nanomaterials composed of two different metals have attracted great attention to harness their unique properties of each element, enabling enhanced performance for various applications. These synergistic effects facilitate the customization for specific applications in the fields of chemistry, catalysis, electronics, and biomedicine. However, even after creating bimetallic nanomaterials, there are still several issues such as biocompatibility, dispersibility, stability and durability. To overcome these limitations, there have been extensive efforts to introduce various ligands to bimetallic nanomaterials. This thesis describes the synthesis, characterization, and biomedical applications of hyaluronate (HA) modified bimetallic nanomaterials of gold (Au) and platinum (Pt). In part I, a bimetallic electrocatalyst of HA-Au@Pt was synthesized to enhance the oxygen reduction reaction (ORR) performance of EBFCs by modifying the electronic structure of Pt with high oxygen reduction. HA is a biocompatible, hydrophilic, and linear polysaccharide, which can be utilized as a binder and stabilizer to enhance dispersibility, stability, and biocompatibility of Au@Pt for wearable and implantable devices. The open circuit voltage was 0.35 V and the maximum current density was -166 μA/cm2 at -0.04 V for the optimized HA-Au@Pt electrocatalyst with 0.5 mM H2PtCl6. In comparison with other biocompatible polymers, HA in HA-Au@Pt catalysts showed excellent dispersibility and remarkable durability under the ORR condition. The power density of a glucose oxidase based EBFC appeared to be 15.8 μW/cm2 at 0.29 V, demonstrating the feasibility of HA-Au@Pt as a promising electrocatalyst in the energy generation of EBFCs. In part II, HA modified Au@Pt bimetallic electrodes were developed for long-term accurate and robust continuous glucose monitoring (CGM) of smart contact lens. After glucose oxidation reaction, the bimetallic electrodes facilitated the rapid decomposition of hydrogen peroxide and charge transfer for robust CGM. The passivation of Au@Pt bimetallic electrode with branch-type thiolated HA prevented the dissolution of Au electrode by chloride ions in tears. In diabetic and normal rabbits, the smart contact lens with HA-Au@Pt bimetallic electrodes enabled the high correlation (ρ = 0.88) CGM with 98.6 % clinically acceptable data for 3 weeks. Taken together, it could be confirmed that the smart contact lens would be successfully used for the stable and long-term CGM with great feasibility for further clinical development. In part III, bimetallic HA-Au@Pt nanoparticles were developed for non-invasive cancer theranosis by near-infrared (NIR) light-mediated photoacoustic imaging (PAI) and photothermal therapy (PTT). The growth of Pt nanodots on the surface of spherical Au nanoparticles enhanced the absorbance in the NIR region and broadened the absorption bandwidth of HA-Au@Pt nanoparticles by the surface plasmon resonance (SPR) coupling effect. In addition, HA facilitated the transdermal delivery of HA-Au@Pt nanoparticles through the skin barrier and enabled the clear tumor-targeted PA imaging. Compared to the conventional PTT via injection, HA-Au@Pt nanoparticles were non-invasively delivered into deep tumor tissues and completely ablated the targeted tumor tissues by NIR light irradiation. Considering all these results, HA-Au@Pt nanoparticles would be successfully harnessed as a NIR light-mediated biophotonic agent for non-invasive skin cancer theranosis. In part IV, bimetallic HA-Au@Pt nanospheres were developed for the targeted theranosis of glioblastoma via NIR guided PAI. The HA-Au@Pt nanospheres showed a red shift in the SPR peak due to the synergistic effect of Au and Pt, which resulted in significant NIR absorption. HA contributed to the stability and biocompatibility of the nanospheres, and facilitated their delivery to brain tumors with overexpressed HA receptors. Under NIR light irradiation, HA-Au@Pt nanospheres significantly improved BBB permeability, demonstrating their potential for brain glioblastoma theranosis via in vivo PAI. In summary, during my Ph.D. thesis, HA-Au@Pt bimetallic nanomaterials have been successfully synthesized and characterized for biomedical applications to biofuel cells, CGM systems on the smart contact lens, and cancer theranosis with PAI and PTT for skin cancer and glioblastoma. These efforts would greatly contribute to open a new big avenue for the development of bimetallic nanomaterials for various biomedical applications.