Fabrication Of Polymeric Drug-Loaded Hybrid Nano-Systems And Their Applications In Tumor Theranostics

Recently, with the development of nanotechnology in biomedicine, nanotheranostics have opened up a new research area to integrate tumor diagnosis and therapy. Nanotheranostics with highly sensitive imaging and targeting properties do not only achieve maximum efficiency in diagnosis and therapy, but can also overcome the problems of side effects and drug resistance. Multifunctional hybrid nanomaterials with good designability, high therapeutic efficiency and biocompatibility can be fabricated from organic and inorganic nanomaterials to become an ideal nanotheranostic for tumor therapy. However, it is still a challenge to design and fabricate a simple and efficient multifunctional hybrid drug-loaded nano-system for theranostics.In this dissertation, we demonstrate the fabrication of three different kinds of novel multifunctional polymer hybrid nanomaterials as theranostics which include:i) biodegradable polymeric hybrid nanoparticles with uniform and controllable size, ii) liposome-coated multifunctional gold nanocages and iii) polymer/gold nanoparticles hybrid assemblies. We also investigated their potential applications for tumor theranostics. This dissertation includes:1. Fabrication of biodegradable polymer hybrid nanoparticles with uniform and controllable size. We developed a hand-driven membrane-extrusion emulsification route and a self-organized precipitation strategy for the preparation of biodegradable polymer hybrid nanoparticles with uniform size. Both size and size distribution of nanoparticles were effectively controlled by manipulating experimental parameters. Furthermore, quantum dots, magnetic nanoparticles and anti-tumor drugs can be encapsulated simultaneously in the polymer nanoparticles. Quantum dots and magnetic nanoparticles-loaded biodegradable nanoparticles were applied in fluorescence/magnetic resonance imaging and magnetic field guided targeting. Our drug-loaded nanoparticles exhibited high drug encapsulation efficiency and excellent release performance. In addition, these drug-loaded nanoparticles also showed higher cytotoxicity towards tumor cells as compared to naked drug. Our surfactant-free nanoparticles from self-organized precipitation, showed higher cellular uptake and better biodistribution as compared to surfactant-coated nanoparticles. These work demonstrated two simple and efficient strategies to prepare uniform biodegradable nanotheranostic materials which provide useful information for further research.2. Fabrication of liposome-coated multifunctional gold nanocages. Uniform hollow porous gold nanocages were prepared by polyalcohol reducing and galvanic replacement method. Liposomes were coated onto the surface of the gold nanocages in order to increase their biocompatibility and avoid drug leakage. A targeted antibody was tethered to the surface of the liposomes by chemical modification to obtain dendritic cells-targeted gold nanocages while immune adjuvant phospholipids were inserted into the liposome membrane to increase the immune response. In addition, immune antigen peptides and photosensitizers can be loaded into the gold nanocages through a solvent diffusion method. These hybrid gold nanocages acted as drug carrier, photothermal agent and imaging agent, were applied in immuno/photothermal-combined therapy and photothermal/photodynamic/ immuno-combined therapy. These liposome-coated gold nanocages with good synergistic therapeutic and optical imaging properties can be used as efficient theranostic agents in tumor therapy.3. Fabrication of polymer/gold nanoparticles hybrid assemblies. Supramolecule directed assembly or two-dimensional confined assembly was employed to prepare the cylindrical polymer/gold nanoparticles nano-assemblies. A new method was employed to precisely control the gold nanoparticles distribution in cylindrical micelles by controlling the chemical properties of the polymer ligands on the surface of the gold nanoparticles. The volume fraction and size of gold nanoparticles along with the supramolecular domain size were investigated systematically to elucidate their influence on the distribution of the gold nanoparticles and the structure of the aggregates. Furthermore, we developed a facile yet efficient route to prepare the hierarchical polymer-tethered gold nanoparticles assemblies with novel morphologies under two-dimensional cylindrical confinement. The confined effect played a key role in determining the structure of the assemblies and the interparticle spacing, which tuned the optical properties of the hybrid assemblies. Due to the strong surface plasmon resonance property, these hybrid assemblies showed good dark-field imaging and photothermal conversion properties. Our results offer experimental guidance for the fabrication of functional hybrid nanoassemblies, which could be potentially useful in tumor nanotheranostics.In summary, we present the preparation of three kinds of multifunctional hybrid nanomaterials and their potential applications as tumor theranostics. Our work may provide experimental guidance and pave the way for the design and synthesis of effective nanotheranostics in future research.