Preparation Of Therapeutic Nanoplatform Based On ZIF-8 With Chemo-photothermal Properties And Performance Evaluation

In recent decades,cancer has become one of the major problems for medicine,which is difficult to be cured and controlled.At the same time,the development of nanomaterials provides a new opportunity for cancer treatment.Compared with traditional materials,nanomaterials has better physical characteristics including optics,magnetism and higher specific surface area,and then widely used as drug-deliver,magnetic resonance imaging contrast agent.Among them,therapeutic nanoplatform which are formed by photothermal therapy and drug-deliver has been a major issue in scientific research,at the same time,the lipidosome and silica as support materials are instability and recalcitrant.Given the above background,in order to synthesis a new multi-functional nanomaterial that integrate drug-deliver and photothermal therpy,we design several photothermal materials incorporating ZIF-8 considering various factors,such as the toxicity and degradation to study the synergistic effect between drug release and photothermal therapy in cancer treatment and made the following research:1.Preparation of ZIF-8 Coated Gold Nanorods/DOX Nanocomposite and Performance EvaluationZIF-8 coated gold nanorod(Au NRs@ZIF-8)was first prepared by stober method in this chapter and optimized by using different ratio of mix solvent.Then,we research the drug-loading capacity of Au NRs@ZIF-8 and pH-induced drug-release process.Based on the thermal transfer characteristics of Au NRs,we further measure the photothermal effect of Au NRs@ZIF-8.Finally,the cell experiment and animal experiments examine the photothermal properties and the drug controlled release performanceof Au NRs@ZIF-8.Conclusions as follows:(1)Au NRs@ZIF-8 are prepared in mixed solvent(methanol:water = 3:2)with an average size of 150nm and present a core-shell construction;(2)Au NRs@ZIF-8 is a photothermal material of high performance;(3)The loading efficiency of Au NRs@ZIF-8 reaches 91.5%and the release curve of DOX in different buffer solution and the TEM images of Au NRs@ZIF-8 or ZIF-8 under the corresponding conditions show that pH can induce ZIF-8 decomposition and then promote the release of DOX;(4)Compared with Au NRs@ZIF-8,DOX is more toxic to MCF-7 cell.The photothermal imaging figure and photographs of animals can prove the synergy of chem-photothermal therapy,but need further verification.2.Preparation of ZIF-8 Coated CuS/DOX Nanocomposite and Performance EvaluationIn order to avoid the complexity of the Au nanorods surface modification in the last chapter,CuS and CuS@ZIF-8 nanoparticles are prepared using solvothermal method and then we research the drug-loading capacity and photothermal effect of CuS@ZIF-8.After that,considering the pH could induce CuS@ZIF-8 decomposition,we further study the release of DOX under the influence of laser and temperature.Finally,the cell experiment and animal experiments examine the photothermal properties and the drug controlled release performance of CuS@ZIF-8.Conclusions as follows:(1)CuS and CuS@ZIF-8 nanoparticles are prepared by solvothermal method with average sizes of 9nm and 104nm,and present relatively uniform spherical;(2)The loading efficiency of CuS@ZIF-8 reaches 98.6%;(3)Compared with temperature and pH-induced,laser-induced can speed up the release of DOX and lead to the dissociation of CuS@ZIF-8.In order to explain the phenomenon,we put forward the possible mechanism and prove the credibility of mechanism through comparing with the appearance of Au NRs@ ZIF-8 after treated with the laser irradiation;(4)The cell/animal experiment and the confocal laser scanning microscope can better understand the influence of DOX on MCF-7 cell.What's more,the photothermal images of model mice and the photos of mice after the treatment can prove the synergy of chem-photothermal therapy from the perspective of qualitative and quantitative.3.Exploring the way to Prepare Quantum Dots(CdSe)Dopped ZIF-8 Coated CuS Nanocompositewe introduce a new fluorescent material-quantum dots to explore the way to integrate fluorescence tracer,drug-deliver and photothermal into a multi-functional composite nanomaterials.First of all,CdSe quantum dots can be prepared in a shorter time using solvothermal method.Secondly,CdSe quantum dots dopped CuS@ZIF-8 can be synthesized by one-step.Conclusions as follows:(1)The averge size of quantum dots are mainly concentrated 4.7 nm,showing strong orange fluorescence;(2)the TEM of CdSe quantum dots dopped CuS@ZIF-8 show that the CdSe quantum dots in methanol appeared a certain degree of reunion phenomenon,therefore,the focus of the next step is to fixthe problems aboutsurface modification of CdSe quantum dots.Because of timelimited,we just do some exploration for thesynthesis of materials and the next step of research will be continued by other members.