Some Studies Of Nanomaterial-Assisted Nonlinear Optical Bioimaging And Light-Mediated Cancer Therapy

Nowadays, cancer has been a great threat to human health. A great many researchers have focused on the development of advanced technologies to perform quick and accurate diagnoses and efficient therapy of cancer. Optical bioimaging has been one of the most useful methods to help scientists to explore the pathogenesis of tumors and diagnose various tumors.In recent years, light-mediated tumor therapy has attracted considerable attention, due to its minimal invasiveness and efficient therapeutic effects. With the continuous advancements in nanotechnology, nanomaterials with unique physicochemical properties, ease of synthesis and functionalization, and high biocompability have been widely used in the biological and medical applications.This thesis focuses on the study of nanoparticle-assisted nonlinear optical bioimaging and light-mediated tumor therapy. The main contents are as follows:1. Synthesis and characterization of gold nanomaterials. Several methods to synthesize gold nanorods (GNRs) that would be bused in the next studies are introduced. In addition, we developed a novel protocal for the one-pot synthesis (seedless) of GNRs using dopamine as a reducing agent. In this method, the concentration of CTAB can be reduced to 22 mM and only 30 minutes are required to complete the synthesis. Furthermore, the longitudinal surface plasmon resonance of GNRs can be tuned from 700 to 1050 nm with a high-yield (80-95%).2. We compared the multiphoton luminescence (MPL) of GNRs with two different aspect ratios, under the excitation of femtosecond (fs) lasers with wavelengths at 1000 nm and 760 nm, respectively. Concerning in vivo blood vessels imaging in mouse brain, the three-photon luminescence (3PL) imaging depth of GNRs under 1000 nm fs excitation could reach 600 μm, which was approximately 170 μm deeper than the two-photon luminescence (2PL) imaging depth of GNRs with a fs excitation of 760 nm. Furthermore, GNRs, which were intravenously injected into mice via the tail vein and accumulated in major organs and tumor tissue, showed high image contrast due to distinct 3PL signals and low background noise upon irradiation of a 1000 nm fs laser.3. We developed a simple and versatile nanoplatform based on biologically inspired polydopamine (PDA) capped gold nanorods (GNR-PDA). Methylene blue [MB, a type of photosensitizer for photodynamic therapy (PDT)] and doxorubicin (DOX, a type of drug for chemotherapy) were directly adsorbed on GNR-PDA via electrostatic and/or π-π stacking interactions, forming GNR-PDA-MB and GNR-PDA-DOX nanocomposites, respectively. We further demonstrated the combined dual-modal light-mediated therapy, by using GNR-PDA-MB nanocomposites [PDT/photothermal therapy (PTT)] and GNR-PDA-DOX nanocomposites (Chemo/PTT). Both of them showed remarkable cancer cell killing efficiency in vitro and significant suppression of tumor growth in vivo, which were much more distinct than any single-modal therapy strategy.4. We fabricated a positively charged polyelectrolyte (PAH) coated barium titanate (BaTiO3, BT) nanoparticles (BT-PAH) with improved colloidal stability and enhanced cellular uptake efficiency. Furthermore, Ce6, a type of photosensitizer for PDT, was sucessfully loaded on BT-PAH to form BT-Ce6-PAH nanocomposites. Enhanced PDT efficiency was achieved due to higher cellular uptake of Ce6 assisted by BT-PAH nanocomposite-loading, which is confirmed by second harmonic generation (SHG) and fluorescence cell imaging. Our work illustrated that BT-PAH nanoparticles can serve as promising contrast agents for SHG imaging and highly efficient nanocarriers for SHG imaging-guided photodynamic therapy.5. We developed an efficient dual-loaded multifunctional nanocarrier for combined photodynamic therapy and chemotherapy based on polydopamine nanoparticles. Methylene blue and doxorubicin were loaded on the PDA nanoparticles at the same time via electrostatic and/or π-π stacking interactions, forming PDA-PEG-MB/DOX nanocomposites. The in vitro and in vivo anti-tumor studies showed that synergistic PDT and chemotherapy effects were pronounced.