| Cancer is a huge public health threat to mankind.For cancer treatment,chemotherapy is still one of the most commonly used antitumor methods in clinical practice.However,the non-specific distribution of traditional drugs inevitably leads to side effects such as severe systemic toxicity.Therefore,the specific targeted delivery of anticancer drugs to tumor sites without damaging normal tissues has been a hot research topic.With the development of materials science and nanomedicine,drug delivery systems have provided new avenues for cancer therapy by enhancing the cellular internalization level of carriers to improve therapeutic efficacy and reduce the side effects of anticancer drugs.Among the choices of these nanocarriers,mesoporous silica nanoparticles(MSNs)show a series of remarkable advantages that have attracted extensive attention.Therefore,two drug delivery system based on mesoporous silica was constructed in combination with different tumor treatment methods in this paper.The main research contents are as follows:(1)In this project,a drug delivery system based on mesoporous silica was designed and prepared.The disulfide bonds were grafted on its surface,while doxorubicin(DOX)and chlorin e6(Ce6)were loaded,and finally,carboxymethyl was coated which constructed the DOX/Ce6@MSN-SSCMCS(DOX/Ce6@MSC)drug-loading system.The successful synthesis of DOX/Ce6@MSC was demonstrated by means of scanning electron microscopy(SEM),ultraviolet-visible absorption spectroscopy(UV),infrared absorption spectroscopy(FT-IR),etc.The cellular uptake demonstrated that DOX/Ce6@MSC could effectively enter cancer cells and successfully release DOX and Ce6,effectively inhibiting the proliferation of human breast cancer cells(MCF-7 cells).Cytotoxicity experiments showed that the inhibitory effect was stronger as the concentration increased.Among them,when the concentration of 20μg/m L,compared with the 25 % cell survival rate of DOX/Ce6@MSC group,the cell survival rate of DOX/Ce6@MSC combined with 660 nm laser irradiation was only 14%,confirming that Ce6 can effectively produce reactive oxygen species and is able to inhibit cell proliferation and induce cell death.Analysis of in vivo antitumor results in tumor-bearing mice showed that DOX/Ce6@MSC could effectively inhibit tumor cell growth under 660 nm laser irradiation,and had no toxic side effects on the mice themselves.The results showed that the synthesized DOX/Ce6@MSC showed good dispersion,stable size,and consistent spectral properties.DOX/Ce6@MSC showed excellent antitumor ability in combination with photodynamic therapy,and could effectively inhibit tumor cell proliferation and induce apoptosis efficiently in vitro and in vivo.(2)In order to improve the targeting of the drug delivery system,this topic further constructed a nano-drug delivery system 3-Br PA/ICG@MSN-FA,which is loaded with 3-bromopyruvate and indocyanine green(ICG)on folic acid-modified mesoporous silica.Through the analysis of photothermal performance experimental results,it can be seen that the heat transfer time constant of 3-Br PA/ICG@MSN-FA is 211.1,and the photothermal conversion efficiency reaches 40.5 %,showing good photothermal performance.The cytotoxicity of normal mouse fibroblasts(MEF cells)by CCK-8 assay showed that MSN-FA had good biological safety,and the unloaded MSN-FA hardly affected the survival rate of cells.The results of cytotoxicity experiments on human gastric adenocarcinoma cells(HGC cells)showed that under the same concentration of 3-Br PA/ICG@MSN-FA,the combined near-infrared illumination group had a lower cell survival rate.Among them,the cell viability of 200 μg/m L 3-Br PA/ICG@MSN-FA was 59.4%,while that of3-Br PA/ICG@MSN-FA+NIR group was 38.6% with same concentration.At the same time,in vivo mouse imaging experiments showed that under near-infrared 808 nm laser irradiation,3-Br PA/ICG@MSN-FA could rapidly heat up and generate a large amount of heat to induce tumor cell apoptosis.The results of in vivo activity experiments in mice showed that3-Br PA/ICG@MSN-FA also had an excellent inhibitory effect on tumor growth.Compared with the tumor weight of 0.1884 g in the blank group,the 3-Br PA/ICG@MSN-FA treatment group was only 0.0789 g,while the tumor weight of mice in the combined photothermal treatment group was lower,reaching 0.0202 g.The results of organ HE staining showed that 3-Br PA/ICG@MSN-FA had no damage to normal tissues and organs.Therefore,the targeted drug delivery system 3-Br PA/ICG@MSN-FA was successfully synthesized,and the combined application of 3-Br PA antitumor therapy and ICG photothermal therapy effectively inhibited tumor cells proliferation.In summary,two nano-drug delivery systems were successfully synthesized based on mesoporous silica nanoparticles,namely the passive targeting nano-drug delivery system DOX/Ce6@MSC and the active folic acid targeting drug delivery system 3-Br PA/ICG@MSN-FA;which successfully realized tumor drug chemotherapy combined with photodynamic therapy and 3-Br PA combined with photothermal therapy,both of which effectively inhibited tumor proliferation and exerted good anti-tumor activity,which provided a potential treatment option for antitumor combined therapy. |
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