| Cancer,a disease with a high mortality rate,has become one of the biggest global healthy challenge in the world.Compared to clinically used cancer treatments,photothermal therapy(PTT),which can employ photothermal agents to generate hyperthermia to precisely "boil" cancer cells.PTT is increasingly recognized to be one of the most potential therapies due to its non-invasiveness and high selectivity.Unfortunately,single PTT cannot completely eradicate tumors due to unavoidable light scattering and and absorption effect in cancer tissues.On the other hand,chemotherapy is considered as the common therapeutic approach to treatment cancer,but chemotherapy alone can't be effectively used in cancer treatment due to drug resistance as well as recurrence and metastasis of tumor.To this end,photothermal-chemo co-therapy has been proved to be an efficient approach to enhance therapeutic efficiency and reduce side effects.In addition,metal chalcogenides has been demonstrated as an apromising photothermal agent for NIR light induced PTT of cancer cells due to its high photothermal conversion effiency and excellent biocompatiblity.However,limited metal chalcogenides have been explored as both photothermal agents and drug carriers up to now for combined photothermal-chemo cancer therapy.The main contents and results of this dissertation are described in two parts as below:1)PEGylated cuprous telluride nanocrystals(PEGylated Cu2Te NCs)were prepared as a novel drug nanocarriers for combined photothermal-chemo treatment of cancer cells.PEGylated Cu2Te NCs were fabricated through a simple two-step process,comprised of hot injection and thin-film hydration.The as-prepared PEGylated Cu2Te NCs(average diameter of 5.21 ±1.05 nm)showed a noticeable photothermal conversion efficiency of 33.1%and good capacity to load hydrophobic anti-cancer drug.Due to the protonated amine group at low pH,the doxorubicin(DOX)-loaded PEGylated Cu2Te NCs(PEGylated Cu2Te-DOX NCs)exhibited an acidic pH promoted drug release profile.To gain insight into how pH and laser irradiation affect drug release,a three-parameter model was used to study DOX release.Based on the results from in vitro cell study,PEGylated Cu2Te-DOX NCs revealed remarkably photothermal-chemo synergistic effect to HeLa cells,attributed to both the PEGylated Cu2Te NCs mediated photothermal ablation and enhanced cellular uptake of the drug.Thus,these results highlighted the potential of Cu2Te NCs as a novel drug carrier for combinational photothermal-chemo therapy to realize efficiently cancer cells elimination.2)Ultrasmall polyacrylic acid functionalized Ni0.85Se nanoparticles(PAA-Ni0.85Se NPs)were prepared as a multifuctional theranostic agent for combined photothermal-chemo treatment of cancer.PAA-Ni0.85Se NPs were synthesized through a facile ambient aqueous precipitation approach.Without showing noticeable in vitro and in vivo toxicity,the as-prepared PAA-Ni0.85Se NPs(average diameter of 6.40±1.89 nm)showed a considerable near-infrared(NIR)absorbance and high photothermal conversion efficiency of 54.06%,which could induce remarkable photoacoustic signals for tumor imaging and heat for localized ablation of cancerous cells upon exposure to NIR light.Notably,the ultrasmall PAA-Ni0.85Se NPs,unlike conventional nanomaterials with larger sizes,showed reasonable body clearance within 8 h after intravenous injection.Furthermore,ascribed to protonation process of amino groups in DOX molecules and carboxyl groups in PAA molecules in an acidic microenvironment,the DOX-loaded PAA-Ni0.85Se NPs(PAA-Ni0.85Se-DOX NPs)revealed promoted drug release at acidic pH,which could be useful for acidic tumor microenvironment responsive drug delivery.Evident from the results of cell-killing assay in vitro and tumor treatment study in vivo,PAA-Ni0.85Se-DOX NPs exhibited evident synergistic effects on killing 4T1 breast cancer cells.Thus,we present a novel type of ultrasmall theranostic agent composed of ultrasmall PAA-Ni0.85Se NPs for potential cancer treatment without long-term toxicity concerns. |
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