Preparation Of Multifuctional Nanoparticles For Drug Delivery And Performance Research

Nanomaterials are widly used in biomaterial application for their unique properties and are significant for the treatment of cancer.Multifunctional nano drug carriers can not only achieve the targeted therapy of chemical drugs,but also synergize a variety of treatments,such as thermal therapy,ultrasonic therapy,radiation therapy etc.They have much important application in biomedical field.Recently,functional nano drug delivery system have been widely studied in cancer therapy.In this dissertation,from the drug chemotherapy combined with thermal therapy to improve the effect of cancer treatment and construct the functional nano drug delivery system,three types of functional nano drug delivery system has been successfully synthesized.The drug loading and release properties,synergy of chemotherapy and thermal therapy in cells were investigated in detail.The detailed contents and results are divided into the following several aspects:（1）Mesoporous silica nanoparticles（MSN）with monodisperse have been synthesized using hexadecyltrimethylammonium p-toluenesulfonate（CTAB）as structure-directing agent.Mesoporous silica/oxide graphene quantum dots（MSN/GQDs）composite nanoparticles were built based on electrostatic interactions used in chemotherapy combine photothermal therapy.The size of MSN nanoparticles with branch boroughs were 50 to 60 nm.GQDs wrapped in amino function MSN nanoparticles（MSN-NH₂）to form MSN/GQDs composite nanoparticles which size are similar to the MSN particle and the dispersion is good.The anti-cancer drug doxorubicin（DOX）as model drug,the DOX loading of MSN/GQDs composite nanoparticles are 48μg/mg with pH and temperature response drug release performance.At the same time,the effect of photothermal performance test showed that MSN/GQDs composite nanoparticles have good photothermal performance.The temperature of MSN/GQDs solution with 10 mg/mL within 10 min can rise from 30℃ to 55℃ in infrared irradiation of 2.5W/cm² and 808nm.Cell experiment showed that MSN/GQDs nanoparticles have good biocompatibility and can be swallowed up by cancer cells.MSN/GQDs nanoparticles with DOX loading were swallowed in cancer cells,the cell survival rate significantly lower than the single drug and MSN/GQDs in the infrared irradiation of 2.5W/cm² and 808nm.It showed obvious synergy effect of chemotherapy and photothermal therapy.Therefore,MSN/GQDs composite nanoparticles are important in cancer treatment.（2）Magnetic mesoporous silica/oxide graphene quantum dots（MMSN/GQDs）functional nanoparticles with chemotherapy,magnetic thermal therapy and photothermal therapy for cancer treatment have been synthesized.Fe₃O₄ nanoparticles were prepared by solvothermal method as the core and hexadecyl trimethyl ammonium bromide（CTAB）as the structure-directing agent,magnetic mesoporous silica nanoparticles（MMSN）were synthesized by sol gel method.GQDs were coated to MMSN nanoparticles based on electrostatic effect to form MMSN/GQDs nanoparticles.The size of MMSN/GQDs nanoparticles with good distribution were 100nm.Magnetic thermal test results showed that the temperature of MMSN/GQDs nanoparticles solution with 10 mg/mL can rise from 28℃ to 68℃ within 10 min in the magnetic field strength of 180 Gauss and frequency of 409 kHz.Photothermal test results showed that the temperature of MMSN/GQDs composite nanoparticles solution with 10 mg/mL can rise from 30℃ to 73℃ within 10 min in the infrared irradiation of 2.5 W/cm² and808 nm.DOX as model drug,MMSN/GQDs composite nanoparticles can load DOX（47μg/mg）with pH response drug control release performance and temperature can accelerate drug release rate.The results of cell experiments show that MMSN/GQDs composite nanoparticles have good biocompatibility and can be effectively phagocytosed by cancer cells.MMSN/GQDs nanoparticles have the synergy of magnetic thermal therapy,photothermal theapy and chemotherapy.The effect of MMSN/GQDs composite nanoparticles in the inhibition of cell growth is much better than the single chemotherapy,magnetic heat treatment or photothermal theapy.Therefore,MMSN/GQDs composite nanoparticles with the combination of chemotherapy and thermal theapy can provide new design ideas for cancer treatment and have important application value.（3）GQDs functional metal organic framework nanoparticles（ZIF-8/GQDs）were successfully prepared by one-step method to realize the application of drug control release performance and photothermal therapy in cancer treatment.The size of ZIF-8/GQDs nanoparticles with good distribution were 50-100 nm.Anti-cancer drugs（DOX）can achieve the high loading with 47μg/mg in synthesis process of ZIF-8/GQDs nanoparticles and the dispersion was almost unaffected.ZIF-8/GQDs nanoparticles have good thermal conversion efficiency under infrared irradiation.The temperature of ZIF-8/GQDs composite nanoparticles solution with 10 mg/mL can rise from 30℃ to49.5℃ within 10 min in the infrared irradiation of 2.5 W/cm² and 808 nm.At the same time,ZIF-8/GQDs composite nanoparticles can realize pH control drug release properties with rapid release under acid condition and slower release in neutral or alkaline conditions because ZIF-8 nanoparticles have skeleton structure of pH response.The quantity of drug release can reach more than 80%within 24 h.Cell experiments showed that ZIF-8/GQDs nanoparticles have low toxicity and can be swallowed up by4T1 cancer cells.ZIF-8/GQDs composite nanoparticles showed significant synergistic effects of chemotherapy and photothermal therapy in 808nm infrared irradiation and can improve the effectiveness of cancer treatment.Therefore,ZIF-8/GQDs nanoparticles provide a new carrier for chemotherapy and photothermal therapy of cancer and expand the biomedical application of metal organic framework material.In summary,MSN/GQDs composite nanoparticles have good biocompatibility and drug controll release properties of pH and temperature response.At the same time,nanoparticles have good photothermal performance.MSN/GQDs composite nanoparticles can realize the synergy of chemotherapy and photothermal therapy.MMSN/GQDs composite nanoparticles have good biocompatibility,magnetic thermal performance,photothermal performance and drug controll release performance.MMSN/GQDs composite nanoparticles as a new type of multifunctional nano drug carrier can achieve the multi-mode therapy of chemotherapy,magnetic thermal therapy and photothermal therapy.ZIF-8/GQDs composite nanoparticles not only have good biocompatibility,photothermal performance,drug control release performance and degradation,but also have the synergy of chemotherapy and photothermal therapy.ZIF-8/GQDs composite nanoparticles as a kind of multifunctional nano drug carrier with biodegradation properties can used for multi-functional treatment in cancer.