Synthesis Of Near-infared Dye Doped MOF Nanocomposite And Their Application In Photothermal Therapy/drug-loading

In recent time,cancer has been one of the major diseases that afflict mankind.To overcome the magligant cancer,scientists have put forward the idea of near-infrared photothermal therapy(PTT)for cancer.Near-infrared light can penetrate biotic tissuses,but do no harm to normal cells at the same time to achieve the cancer treatment,and this process is inseparable from the well-behaved near-infrared thermal materials.Firstly,the ideal photothermal materials must have relatively high efficiency of photothermal conversion,and secondly considering that the final clinical application they should be low toxicity,so we chosed the near infrared dye as functional components which are low toxic with high light-heat conversion efficiency.In order to combine PTT with other clinical cancer therapy means,people have developed different kinds of drug carriers to realize the construction of multifunctional diagnosis and treatment platform,such as mesoporous silica or high polymer.But because of the biocompatibility of silica,and the polymer is easy to decompose,we chose metal organic framewoks(MOFs)to build pH responsive drug delivery system(DDS).In view of above background,aiming at building multifunctional nanocomposite with PTT and chemotherapy,we synthes ized the metal organic framewoks which near infrared dye was adulteration in and anticancer drug adriamycin(DOX)was whereafter loaded on to obtain multifunctional nanocomposite.The cell toxicity of the material was evaluated with normal cells,and the material was evaluated in vitro/vivo with the help of cancer cell and tumor xenograft model.The more details of this work are as follows:1.The YHD796 was used as the photothermal component and was coated with the zeolite imidazole framework(ZIF-8)to obtain the YHD796@ZIF 8 nanocomposite.The particle size of the composite material was between 40-100 nm and under the irradiation of near-infrared laser(808 nm,1 W),the temperature of the material can rapidly increase to 50 °C,so it can be used as photothermal therapeutic agent;before and after the mixing of DOX solution with YHD796@ZIF-8,the change of the concentration manifested drug loading efficiency is 2.9 wt%;the release of DOX on YHD796@ZIF-8-DOX was measured in phosphate buffer solutions(pH=5,6,7.4)at different pH;It was found that laser irradiation can greatly accelerate the release of DOX;After evaluation of toxicity and in vitro therapeutic effect,we intratumorally injected the YHD796@ZIF-8-DOX into tumor-bearing mice and treated the tumor with photothermal therapy and chemotherapy,and the tumors were clearly ablation.During the experiment,we also noticed that the particle size was not uniform,and the coating efficiency of the organic functional dye YHD796 in the ZIF-8 was lower than the theoretical value.In addition,the nanocomposite was only focused on the treatment of the tumor rather than the construction of “Integration of diagnosis and treatment”.These problems should be much considered.2.One-step method was used to synthesize ICG@ZIF-8 with good monodispersity and uniform particle size.The size of the synthesized material was about 100 nm;the optical properties and fluorescence characteristics of the material were studied.After a series of characterizations,we verified the photo-thermal conversion capability of ICG@ZIF-8 and confirming that the material can be used as a phototherapy agent,and that ICG encapsulated in ZIF-8 does not have strongly fluorescent like free ICG,but the supernatant can detect intense fluoresce nce after irradiated with laser light;the drug loading on DOX is 1.71%;at the same time,DOX is almost not released in the pH=7.4 PBS solution,and when pH = 5,he release of DOX can reach nearly 60% after three days,and it is found that near-infrared laser can greatly accelerate the release of DOX,and it can reach the equivalent release compared with situation without laser in a short time;we have carried out the live/dead cells staining of the material and MTT to evaluate toxicity and the effect of combined phototherapy-chemotherapy in vitro.Followed by intratumoral injection of the material into the tumor-bearing mice,synergistic treatment of photothermal therapy and chemotherapy achieved good therapeutic effect;based on the fluorescence detection in vitro,we injected ICG@ZIF-8 into model mice and monitored the changes of fluorescence area and intensity of the whole body of the model mice,which proved the application potential as a fluorescent probe.In the first two chapters,nanocomposites YHD796@ZIF-8-DOX and ICG@ZIF-8-DOX have been synthesized and good synergistic therapeutic effects have been achieved,but unavoidable weak toxicity of zinc ions should be considered in the next chapter.3.In order to further weaken the influence of carrier toxicity on normal cells,we selected MIL-100(Fe)coated near-infrared dye IR825,and explored the preliminary synthesis conditions.The experimental results are as follows: UV-visible spectroscopy indicates that IR825 is successfully encapsulated into MIL-100(Fe);IR825@MIL-100(Fe)is synthesized by solvothermal method.The particle adhesion is severe and the crystallinity is low.As a result,the next step of this research still needs to improve the synthesis conditions of IR825@MIL-100(Fe)and solve the stability problem of materials in PBS solution.Due to the limitation of the postgraduate academic system,this work is limited to the synthesis of materials,the follow-up work will be further improved by other students in our group.