Microfluidic One-step Preparation Of Alginate Microspheres Encapsulated With In Situ-formed Bismuth Sulfide Nanoparticles And Their Photothermal Effects

Transcatheter arterial chemoembolization?TACE?is the preferred choice for the advanced liver cancer,but there are still some shortcomings,such as easy to relapse and incomplete embolization.As a supplementary treatment,hyperthermia can kill cancer cells directly by increasing the local temperature of the tumor site up to 42°C and above.In addition,hyperthermia may also increase the sensitivity of tumor cells to radiotherapy and chemotherapy.Therefore,hyperthermia combined with TACE is expected to improve the treatment efficiency of liver cancer.Near-infrared?NIR?mediated photothermal therapy is based on photothermal agents which can absorb NIR light and then convert to heat at the tumor site.The produced heat can kill tumor cells and ablate tumor tissue taking the advantages of targeted,high efficiency and weak side effects.In this thesis,alginate microspheres encapsulated with in situ-formed bismuth sulfide nanoparticles?denoted with Bi₂S₃@BAC?have been prepared by one step using a droplet-based microfluidic technique.The prepared drug-loaded microspheres would integrate multiple therapeutic functions including hyperthermia,embolization and chemotherapy,which were expected to improve the therapeutic efficiency of tumors.The main research contents and results of this thesis are as follows:1.Bi₂S₃@BCA microspheres were one-step prepared using a droplet-based microfluidic chip fabricated of polydimethylsiloxane and glass as a preparation device,an aqueous solution of sulfur-containing compound and sodium alginate as a dispersed phase,liquid paraffin containing CaCl₂ nanoparticles?NPs?and surfactant as a continuous phase,and the aqueous solution containing the surfactant and Bi³⁺ions as a collection bath.The effects of different sulfur sources and their concentrations,the composition of the collection bath on the morphology and stability of the prepared microspheres were studied.As a result,the aqueous solution of Na₂S₂O₃?0.15 mol/L?and sodium alginate?2.0 wt%?was opted as the disperse phase,liquid paraffin containing Span 80?2.0 wt%?and CaCl₂ NPs?0.8 wt%?was used as the continuous phase,aqueous solution of Bi?NO₃?₃?0.3 mol/L?,Ca?NO₃?₂?0.1 mol/L?,Tween 20?2.0 wt%?and O?-10 emulsifier?2.0 wt%?was adopted as the collection bath.The Bi₂S₃@BCA microspheres were prepared with uniform size of approximately 150?m in diameter at a flow rate of 600?L/h and 4800?L/h for the dispersed phase and continuous phase,respectively,which are suitable for use as vascular embolization materials.2.The morphology and composition of the Bi₂S₃@BAC microspheres were characterized by scanning electron microscopy,transmission electron microscopy and X-ray photoelectron spectroscopy,etc.The results showed that the size of the in situ-formed Bi₂S₃ NPs encapsulated in the microspheres were approximately 500 nm.The resultant Bi₂S₃@BAC microspheres exhibited strong absorption of NIR light,which should originate in the encapsulated Bi₂S₃ NPs.In addition,under the laser irradiation of 808 nm with power density of 1.5 W/cm²,the temperature of the suspension of Bi₂S₃@BCA microspheres?10 wt%?was increased by more than 65°C with excellent photothermal effect in vitro.Thus Bi₂S₃@BCA microspheres can be used for hyperthermia of tumors.Furthermore,Bi₂S₃@BCA microspheres had good photostability.3.The anti-cancer drug doxorubicin hydrochloride?DOX·HCl?-loaded microspheres?DOX-Bi₂S₃@BCA?were prepared by a electrostatic adsorption method.The effect of NIR laser irradiation on drug release behavior of drug-loaded microspheres was studied by dialysis method.The results showed that NIR laser irradiation promoted the release of drugs in microspheres.In addition,the results of cytotoxicity experiments showed that chemotherapy combined with photothermal therapy significantly increased the lethality of tumor cells.Therefore,the as-prepared Bi₂S₃@BCA microspheres have multiple functions including hyperthermia,chemotherapy and embolization.