Construction And Drug Loading Performance Of Marine Polysaccharide Functionalized Mesoporous Silica Nano-Delivery System

Cancer is a serious threat to mankind’s health.How to target and efficiently deliver drugs to tumor site is one of the research hotspots in the field of drug delivery.Mesoporous silica nanoparticles(MSN)is an important drug delivery platform due to its adjustable large pore size and high porosity.The MSN can be modified by natural organic molecules to prepare a drug delivery system with intelligent response.Due to its good biocompatibility and biodegradability,marine polysaccharides can be used to functionalize MSN to prepare a kind of intelligent MSN based nano drug delivery system.In this paper,curcumin(cur)with antitumor activity was used as a model drug to prepare two kinds of marine polysaccharides modified mesoporous silica nanoparticles with tumor microenvironment stimulation response.The main contents were as follows:(1)A kind.of core-shell nanoparticles was designed.Firstly,mesoporous silica was aminated to prepare amino mesoporous silica(MSN-NH2),and then alginate oligosaccharides(AOS)were modified on the positively charged core MSN-NH2 for functionalization to obtain MSN-NH2-AOS core-shell nanoparticles.Meanwhile,the loading and transport properties of cur were studied.The MSN-NH2-AOS nanoparticles were characterized by Dynamic light scattering(DLS),thermogravimetric analysis(TGA)and X-ray photoelectron spectroscopy(XPS).The preparation process of MSN-NH2-AOS nanoparticles was optimized,and we the investigated loading rate,entrapment efficiency and in vitro release behavior of curcumin(Cur).The results showed that the loading ratio of MSN-NH2-Cur-AOS nanoparticles to cur was 99.46%.The total release amount was 28.9%under neutral condition,but under acidic condition,the total release amount was 67.5%.The antitumor effect of nanoparticles in vitro was investigated by MTT assay and cell uptake assay.The results showed that MSN-NH2Cur-AOS was more easily absorbed by tumor cells than free cur.When curcumin concentration reached 50 μg/mL,MSN-NH2-Cur-AOS nanoparticles had strong cytotoxicity to tumor cells.(2)Based on fucoidan and mesoporous silica(MSN),a drug loaded nano particle MSN-NH2Cur-SS-FUC containing disulfide bond was designed and prepared by redox reaction between disulfide bond in nano carrier and high concentration GSH in tumor cells.The drug loaded nanoparticles not only have the characteristics of pH sensitive drug release,but also have the characteristics of redox responsive drug release.Therefore,it can achieve targeted drug delivery at tumor sites,promote the accumulation of anti-tumor drugs in tumor sites,and improve the therapeutic effect.The product was characterized by SEM,TEM and FTIR,and we also investigated the loading rate and release behavior of cur from MSN-NH2-CurSS-FUC.The results showed that the entrapment efficiency of MSN-NH2-Cur-SS-FUC for curcumin was more than 90%,and the cumulative release rate of curcumin was more than 80%within 24 hours under the dual stimulation of slightly acidic tumor site and high concentration of glutathione.The nano drug delivery system is suitable for tumor targeted delivery of fat-soluble anti-tumor drugs.