Preparation And Application Of Organic-inorganic Core-shell Nano Drug Carriers

Currently,the deterioration of the environment has led to a sharp increase in the number of cancer patients.Chemotherapy causes less trauma to patients and is widely used.However,due to the increased drug resistance of cancer cells,the side effects of anti-cancer drugs are relatively large,and it is difficult to break through the tissue barrier of tumors,etc.,the treatment effect is poor.Therefore,the development of appropriate drug delivery system or new cancer treatment methods becomes a new way to improve the effect of cancer treatment.In this paper,based on organic-inorganic core-shell nanoparticles,three kinds of nano-drug controlled-release systems with multiple responsive delivery function were developed.The loading capacity and controlled-release performance of doxorubicin hydrochloride（DOX）and potassium persulfate（K₂S₂O₈）were studied,and the cellular uptake and drug accumulation ability of antitumor drugs were evaluated.The specific research contents are as follows:1)Preparation and application of silver/polymer core-shell nanospheres with multiple responses of pH/temperature/reductionA new type of silver nanoparticles（Ag NPs）/poly（N-isopropylacrylamide-co-2-dimethylaminoethyl methacrylate）（PND）core-shell multifunctional composite nanospheres（PND-Ag）with pH/temperature/REdox multi-stimulus response were prepared by two-step one-pot method.PND-Ag had a spherical structure with a particle size of around 200 nm and a surface charge of about-12 mV.It had good dispersibility,excellent multi-sensitive stimulus release performance and good biocompatibility.In the release experiment,the cumulative release rate of the drug in the buffer solution with pH=5.0 reached up to 98%,showing excellent release performance.Cell experiments showed that PND-Ag-DOX had good biosafety and pharmacological activity（IC50 value of PND-Ag-DOX was 1.7 times lower than free DOX）.In addition,compared with the normal cells（COS-7）,cancer cells（CT-26）could fully absorb the compound gel,which indicated that the compound gel had certain specificity and could be used for the imaging of tumor cells.The combination of precious metals and multi-response gels integrates cell imaging and drug delivery,providing support for the integrated diagnosis and treatment technology.2)Preparation and properties of gold nanocage/hyaluronic acid core-shell structure nanocarriers with multiple response of pH/enzyme/photothermalA drug delivery system based on pH/enzyme/photothermal multiple response/combination of chemotherapy and photothermal therapy/CD44 targeting was prepared.DOX@AuNC@HA（DAH）nanoparticles with organic and inorganic core-shell structure were prepared by a simple one-pot method with modified sodium hyaluronate,gold nanocages and doxorubicin hydrochloride.The experimental data showed that the particle size of DAH was about 85 nm,the surface charge was about-15.6 m V,and it had a high drug loading rate（about 11%）and a low leakage rate（about20%in the buffer solution with pH=7.4）.In the photothermal conversion experiment,DAH had high photothermal conversion rate and good stability,which met the requirements of photothermal therapy.When combined with chemotherapy and photothermal therapy,the cell viability of A549 cells was only 12.5%,showing excellent killing efficiency.Furthermore,due to the targeting of hyaluronic acid to CD44 carrier protein on the surface of cancer cells,DHA could be more fully absorbed by cells.Using the combination of the hollow porous structure and photothermal conversion of gold nanocages with the stimulation response and targeting of the organic shell,safe and efficient tumor therapy is realized,providing a new way for the development of low toxicity and high efficiency nano drug delivery system.3)Preparation and application of pH/enzyme-responsive mesoporous silica/hyaluronic acid core-shell nanocarriersChemodynamic therapy（CDT）provides a new strategy for the treatment of cancer.However,the lack of reactive oxygen species（ROS）and the special reductive environment within the tumor limit its further development.Here,we designed a Fe²⁺catalyzed dual free radical treatment system for tumor.Mesoporous silica（MSN）containing K₂S₂O₈ was coated with hyaluronic acid（HA）,and then tannin-iron complex（DF）was modified on the surface of hyaluronic acid through coordination to form organic-inorganic core-shell nanoparticles K₂S₂O₈@MSN@DF（KMHF）.The particle size of MKHF was about 350 nm and the surface charge was about-30 m V.It had excellent stability and biocompatibility.In the simulated cell microenvironment release experiment,the 10 h release rate of K₂S₂O₈ was higher than 70%in response to pH and enzyme stimulation in MKHF,showing the potential of CDT.In addition,since HA had an overexpressed CD44 targeting site on the surface of tumor cells,this will improve the efficiency of particle uptake.Cell experiments also further proved that MKHF could be absorbed by cells well,and had a strong ability to kill cells and value for further development.Therefore,this CDT system,which uses active substances inside and outside the cell to catalyze the generation of two free radicals,will provide strong support for the treatment of cancer.