Polydopamine Nanoparticles/Doxorubicin Hydrochloride Encapsulated Core-shell Microspheres For Locally Combined Photothermo-chemotherapy

With the improvement of human living standards,the human pursuit of material life and the concern for their own health are increasing day by day.However,cancer always threatens the safety of human life.At present,cancer treatment methods include chemotherapy,radiotherapy,surgery,photothermal therapy and so on.In this thesis,comprehensive treatments were used to treat cancer,within which photothermal therapy and chemotherapy are combined for antitumor,effectively reducing toxic side effects caused by single high-dose chemotherapeutic drugs.Specifically,in this thesis,the coaxial electrospraying technique was employed to fabricate core-shell microsphere containing chemotherapy drug(doxorubicin hydrochloride)and photothermal therapy agent(polydopamine nanoparticles)for the localized treatment of cancer.Firstly,the preparation process of core-shell microspheres via coaxial electrospraying was explored.For successfully preparing the core-shell microspheres,the coaxial electrospraying conditions(polymer concentration,external phase flow rate,receiving distance,voltage)were optimized as follows:the polymer concentration is 20 wt%,the external phase flow rate is 0.8 m L/h,the receiving distance is 20 cm,and the voltage of 12 kV.The core-shell structure of the microspheres was confirmed by transmission electron microscopy,cryo-scanning transmission electron microscopy,and laser confocal microscopy.Subsequently,the photothermal properties of polydopamine nanoparticles loaded core-shell microspheres(PDA@PLGA)were investigated.When the concentration of microspheres was 8 mg/m L,the solution temperature rose to 59.8?after the 808 nm(1.5w/cm~2)near-infrared laser irradiating for 10 minutes,indicating that PDA@PLGA microspheres had a photothermal effect which can be used as a photothermal therapy agent.The in vitro DOX·HCl release curves of microspheres(PDA/DOX·HCl@PLGA)loading with polydopamine nanoparticles and doxorubicin hydrochloride was investigated,which shown that the irradiation of near-infrared lasers could accelerate the release of doxorubicin hydrochloride.Furthermore,after drug release for a certain period of time,the morphology of the microspheres were characterized by scanning electron microscopy.It was found that the microspheres in the near-infrared laser irradiation group had significant pores,which indicated that after laser irradiation,the degradation of the polymer was accelerated owing to the increased solution temperature.Then,biocompatibility studies of PDA@PLGA microspheres demonstrated that with the microsphere concentration increased to 8 mg/mL,the survival rates of the cells was about 90%,which demonstrated the safety of the material.Photothermal cytotoxicity studies of PDA@PLGA microspheres demonstrated that photothermal cytotoxicity of the microspheres was concentration-dependent.Meanwhile,the in vitro antitumor study of PDA/DOX·HCl@PLGA microspheres showed that the microspheres loading polydopamine nanoparticles and doxorubicin hydrochloride had better antitumor effects.Finally,the in vivo antitumor effect of core-shell microspheres containing polydopamine nanoparticles and doxorubicin hydrochloride(PDA/DOX·HCl@PLGA)was evaluated.The infrared thermal imaging of mice showed that the photothermal effect of PDA/DOX·HCl@PLGA microspheres was still obvious.While fluorescence imaging and tissue distribution indicated that near-infrared laser irradiation could promote the release of doxorubicin hydrochloride.Changes of tumor volume in mice demonstrated that the PDA/DOX·HCl@PLGA had better antitumor effects under near-infrared laser irradiation,which was also confirmed by the histological analysis.The mice body weight and and survival curves of mice proved that the microspheres containing polydopamine nanoparticles and doxorubicin hydrochloride had good biocompatibility.