Protein - Nanogold Hybrid Microstructure Research In Drug Delivery And Scaffold Materials

Natural proteins have attracted great attention for construction of drug delivery vehicles and functionalized biomedical devices due to their good biocompatibility, biodegradability, and amenability to surface functionality. In addition, gold nanoparticles also gained interest for promising applications including photothermal therapy, biological imaging, sensors, drug and gene delivery systems because of their unique optical response and superior biocompatibility. With the increasing interest for multifunctional nanomaterials or devices in the biomedical field, it is necessary to synthesize novel organic-inorganic hybrid materials which offer additional special functions for drug delivery or other potential medical applications.In this dissertation, silk fibroin and bovine serum albumin (BSA) were chosen as the ideal proteins as organic materials. Subsequently, gold nanospheres and nanorods were synthesized to modify the organic microstructures including capsules and flower-like particles so as to obtain the hybrid multifunctional materials. The mains results are as follows:1. Single component silk capsules with different layers were synthesized from spherical PLGA templates using the layer-by-layer (LBL) technique, which can avoid the introduction of toxic cationic polyelectrolytes. More importantly, we further synthesized two kinds of hybrid capsules:1) gold nanoparticles inside both silk layers;2) DNA-modified gold nanoparticles on the surface. These hybrid capsules have promising applications for controlled release, combination therapy and theranostic medicine.2. Single component silk capsules were synthesized by desolvation method with the PLGA templates removal. The permeability of the capsules was investigated using fluorescence biomacromolecules as the tracer. Moreover, the shell permeability can be finely tuned using gold nanospheres or nanorods, even both of them together. Finally, these hybrid capsules offered distinct surface-enhanced Raman effect. These hybrid capsules can be used as the candidates for theranostic application or integrated therapy of photothermal and chemical therapy.3. BSA flower-like microstructures with special topography were prepared by desolvation method. We confirmed that the architecture of flower was composed of BSA tubes, which were formed via deposition on the flower-like inorganic salts crystal templates by following dissolution of them. Rhodamine B, a model drug, was loaded into flower-like microstructures, which demonstrated that these flower-like particles can be used in drug delivery systems, especially for local drug delivery to the inner ear. 4. The physicochemical and bioactive properties of the above mentioned BSA flower-like microstructures were manipulated by means of introduction of gold nanoparticles or RGD peptides. These novel hybrid microstructures with unique geometry, topology, mechanical and surface chemical properties can be used in future research on cell-material interactions or local drug or cell delivery.In summary, we synthesized single component silk capsules using LBL and desolvation technique, respectively. Subsequently, these silk capsules were modified with gold nanospheres or/and nanorods, which offer these hybrid capsules distinct functions and potential applications including combination therapy, theranostic medicine and trace imaging agen by introduction of DNA, gold and silk capsules. In addition, we prepared BSA flower-like microstructures by desolvation and modified them with deposition of gold nanoparticles and RGD. In one word, these hybrid materials including microcapsules and flower-like microstructures can serve as a basis of research on the potential drug or cell delivery.