Construction And Effect Evaluation Of Bismuth Based Nanodrug Delivery System For Enhancing Gambogic Acid Effect

The treatment of cancer has always been the focus of scientific research.Chemotherapy is a common cancer treatment method,it is effective for a variety of cancers,but it has many limitations,such as high side effects and low bioavailability.The development of nanoscience has greatly promoted the diversified the advance of nanomedicine carriers.Nanocarriers can not only improve drug efficacy and reduce the side effects of chemotherapy,various types of nanocarriers also have therapeutic effects such as photo thermal therapy(PTT)and photo dynamic therapy(PDT).More favorably,a variety of nanocarriers also have the function of imaging mode enhancers such as Computed Tomography(CT)Imaging and Nuclear Magnetic Resonance Imaging(NMRI).Bismuth-based nanocarriers have attracted more and more attention because of its wide absorption in the near-infrared region and the high atomic number of Bi element which can mediate CT imaging.Among of bismuth-based nanocarriers,bismuth tungstate(Bi2WO6)nanocarriers have unique advantages in tumor treatment because of their photocatalytic activity,but the research results are few.Therefore,this study intends to prepare a mesoporous structure bismuth tungstate(mBi2WO6)nano-drug carrier having a photothermal effect.The carrier will be used to load gambogic acid(GA),a chemotherapeutic drug,which can also inhibit heat shock protein function and reduce cell heat tolerance.Our research will utilize the photothermal and photocatalytic activity of the bismuth tungstate carrier combined with GA to achieve efficient inhibition of tumor cells.Firstly,we explored and optimized the preparation conditions of mesoporous bismuth tungstate(mBi2WO6)nanocarriers.Bismuth trioxide(Bi2O3)nanospheres were prepared by hydrothermal synthesis though the recrystallization of Bi atoms.The morphology was observed by electron microscopy.The prepared Bi2O3 nanosphere is a solid spherical structure with an average particle size of about 187.33±26.65 nm.Hollow bismuth tungstate(Bi2WO6)nanospheres were prepared though Bi2O3 nanospheres as a sacrificial template by Kirkendall effect.The Bi2WO6 nanospheres were also analyzed and characterized,and the prepared Bi2WO6 was a hollow spherical structure with an average particle size of about 214.54±24.83 nm.The average particle size of Bi2WO6 nanospheres is similar to the distribution range of the template,indicating that the external dimensions are not changed during the hollowing process.However,the hollow structure Bi2WO6 nanoparticles have weak light absorption in the Near Infrared(NIR)region.In order to improve the light absorption of the carrier in the near infrared region,after surface modification of the hollow structure Bi2WO6,the Bi2WO6 was reduced with sodium borohydride(NaBH4)using a one-step reduction method to obtain the target product,the mesoporous bismuth tungstate(mBi2WO6)nanocarrier.Secondly,the prepared mBi2WO6 was subjected to morphology,element composition,ultraviolet-visible light absorption detection etc.characterization and photothermal conversion performance test.The morphological characterization results show that the surface of mBi2WO6 is rough,rich in mesoporous pores and granular materials on the surface.The average particle size distribution is 190.46±23.34 nm,which is basically consistent with the template particle size distribution.The characterization analysis results of elements through Mapping surface scan and EDS showed that the prepared mBi2WO6 nanomaterials were mainly composed of three elements:Bi,O,and W.According to the XPS results,it is speculated that the oxygen vacancy structure in mBi2WO6 is formed by the reduction of NaBH4 resulting in the removal of oxygen atoms in[WO4]2-.The XRD analysis results show that the surface distribution of mBi2WO6 is mainly Bi element.The SEAD crystal structure analysis results show that the mBi2WO6 is a polycrystalline structure.Based on the results above we speculated that the Bi element and the internal Bi2WO6 crystal has formed a Bi-Bi2WO6 heterojunction structure,which lead to greatly improved photothermal conversion performance of mBi2WO6.The photothermal conversion efficiency of mBi2WO6 in the NIR region is 43.95%,indicating the as prepared mBi2WO6 is capable for PTT.Finally,we have explored the drug loading conditions of mBi2WO6 loaded with GA.The drug loading efficiency of GA@mBi2WO6 was preliminary optimized to 7.43%.Human umbilical vein endothelial cell(HUVEC)and mouse breast cancer cell A549 were used as cell models to explore the biocompatibility of mBi2WO6.The results show that mBi2WO6 has no significant inhibitory effect on HUVEC cell viability,the cell viability is above 80%even at the concentration of 200μg/mL,while it has a significant inhibitory effect on A549 cell viability.This shows that the prepared mBi2WO6 has good biocompatibility and cell selectivity.The ability of mBi2WO6 and GA@mBi2WO6 to inhibit the proliferation of cancer cells with or without 808 nm laser irradiation was studied.The results show that GA@mBi2WO6has a better inhibitory effect on cancer cells under 808 nm laser irradiation while significantly reduce GA dosage.In summary,this study prepared a mesoporous bismuth tungstate nanocarrier(mBi2WO6)with a new structure.The bismuth tungstate nanocarrier has high photothermal conversion efficiency and relatively stable photothermal heating performance.The mesoporous structure endows the ability of mBi2WO6 as drug carrier.The prepared nanoparticles can play the role of PTT and combine with the chemotherapeutic effect of GA to achieve synergistic treatment of tumors.This research provides theoretical support for the preparation of bismuth tungstate based nano-drug delivery systems and emerging cancer treatments in the future.