Synthesis Of Photothermal Conversion Nanocomposites For Photothermal/Chemotherapy

Photothermal therapy(PTT)technology that uses optical absorbing agents to convert absorbed near-infrared light energy into local hyperthermia to kill cancer cells,is an emerging method for cancer treatment.This technique is effective,easy to operate,and non-invasive.The synergistic treatment of PTT and chemotherapy can be realized via constructing nanocomposites based on PTT agents,possessing a better therapeutic effect.As an important part of supramolecular chemistry,supramolecular macrocycles could bind to guest molecules in their cavities through specific non-covalent bond interactions.They have also been modified on inorganic materials with optical,electrical or magnetic properties,expanding their applications in catalysis,sensing,and drug delivery.The introduction of supramolecular chemistry into PTT agent is expected in the design and synthesis of multifunctional nanocomposites to achieve synergistic treatment.Thus,we firstly constructed AIEgen-functionalized mesoporous silica nanocomposites gated by cyclodextrin-modified Cu S for cell imaging,PTT,and drug delivery in the thesis;Secondly,a supramolecular nanosystem for targeted PTT and chemotherapy was constructed based on pillararene-stabilized Cu S nanoparticles;Finally,Mn WO4 nanoparticles coated by polydopamine was developed to be an effective PTT agent.The main results are summarized as follows:(1)Fluorescent AIEgen-containing mesoporous silica nanoparticles(FMSN)were prepared by the coprecipitation method.Meanwhile,per-6-thio-?-cyclodextrin(CD)was modified on Cu S nanoparticles via ligand exchange,and as prepared CD-Cu S nanoparticles were anchored on the surface of benzimidazole-grafted FMSN(FMSN@Cu S),acting as a photothermal agent and gatekeeper.After irradiation with laser at 808 nm for 7 min,the elevated temperature of the dispersed solution of FMSN@Cu S in the concentration range of 50-800 ?g/m L was 5-28 °C;there was no noticeable difference in the photothermal conversion efficiency upon periodic NIR laser ON/OFF irradiation for five repeat cycles,demonstrating high photothermal stability of FMSN@Cu S.Anticancer drug,doxorubicin hydrochloride(DOX),was loaded into FMSN@Cu S,and zero prerelease at physiological p H(7.4)and on-demand drug release in an acidic environment have been achieved due to the p H-responsive gate-opening of CD-Cu S and the better water solubility of DOX in an acidic condition.The FMSN@Cu S nanocomposite can generate obvious thermal effect after the exposure of 808 nm laser,which also accelerated the DOX release.More importantly,DOX-loaded FMSN@Cu S displayed efficient anticancer effects in vitro upon 808 nm laser irradiation,demonstrating a good synergistic therapeutic effect via combining enhanced chemotherapy and photothermal therapy.Besides,blue-emitting FMSN@Cu S exhibited good cell imaging capability,and the intracellular drug delivery process of DOX-loaded FMSN@Cu S have been tracked according to the change of luminescence intensity.(2)A smart supramolecular nanosystem integrating targeting,chemotherapy,and photothermal therapy was constructed based on carboxylatopillar[5]arene(CP[5]A)-functionalized Cu S nanoparticles(Cu S@CP NPs).Cu S@CP NPs with good monodispersibility and strong near-infrared absorption(700-1100 nm)were synthesized in aqueous solution through a facile one-pot supramolecular capping method.After irradiation for 7 min,the temperature elevation of Cu S@CP solution in the concentration range of 14.5-174 ?g/m L was about 10-44 °C,and the photothermal conversion efficiency of Cu S@CP was calculated to be 34%.Meanwhile,liver cancer-targeted galactose derivative(G)with pyridine moiety was prepared,which can form supramolecular complex with CP[5]A ring.The association constant(Ka)of G and CP[5]A was determined to be(1.07 ± 0.24)× 104 M-1 through NMR titration experiments and the nonlinear curve-fitting method.Thus,G molecules were installed on Cu S@CP via the strong host-guest binding interaction.The resulting smart supramolecular nanosystem,namely,Cu S@CPG,exhibited excellent photothermal ablation capability to Hep G2 cells upon irradiation with laser at 808 nm.Chemotherapeutic drug,DOX,was further loaded on Cu S@CPG via electrostatic interactions between positively charged DOX and negatively charged CP[5]A to give Cu S@CPG-DOX with a high drug-loading capacity up to 48.4%.The weakening of DOX-CP[5]A interactions in an acidic environment promoted the p H-responsive drug release from Cu S@CPG-DOX.Significantly,this multifunctional supramolecular nanosystem showed a remarkably enhanced therapeutic effect through the combination of targeted chemotherapy and photothermal therapy upon in vitro cell study.Moreover,preliminary in vivo study demonstrated that Cu S@CPG and Cu S@CPG-DOX had good biocompatibility and excellent tumor inhibition effects upon 808 nm laser irradiation.(3)Glycine-modified Mn WO4 nanoparticles were synthesized via the hydrothermal method.Dopamine hydrochloride accumulated on the surface of Mn WO4 nanoparticles and further polymerized to obtain polydopamine-coated Mn WO4 nanocomposite(Mn WO4@PDA)in an alkaline environment.Mn WO4@PDA nanocomposite exhibited obvious absorption in the NIR region derived from PDA.After irradiation with 808 nm laser for 7 min,the elevated temperature of the dispersed solution of Mn WO4@PDA in the concentration range of 50-1000 ?g m L-1 was 9.4-35.7 °C.Moreover,in vitro cell experiments and histology analysis of the heart,liver,spleen,lung,and kidney stained with hematoxylin-eosin(H&E)showed good biocompability of the Mn WO4@PDA nanocomposite.Meanwhile,Mn WO4@PDA nanocomposite(? 200 ?g/m L)exhibited excellent photothermal ablation capability to Hep G2 cells under 808 nm laser(10 W/cm2)irradiation for 7 min,suggesting that it can be used for the further in vivo study of photothermal therapy and MRI/CT imaging.