Biological Evaluation Of Mesoporous Silica Nanoparticles Based On FRET And Redox-responsive For Drug Delivery System

The release of anti-cancer drugs at targeted sites can maximize the therapeutic effect of malignant tumors and reduce the toxicity to healthy cells.However,there is still a lack of stimuli-responsive nanocarriers for real-time monitoring of anticancer drugs,especially non-fluorescent drugs.Therefore,a fluorescence-responsive energy transfer(FRET)-based stimuli-responsive drug delivery system loaded with 6-mercaptopurine(6-MP)as a model drug was designed for drug targeting and real-time monitoring in cancer therapy,in which the hyaluronic acid(HA)as target ligand labeled with rhodamine was modified on the surface of the fluorescent mesoporous silica nanoparticles containing zinc 8-hydroxyquinolinate complexes by the cleavable disulfide bonds.The morphology,particle size,potential,fluorescence characteristics,in vitro drug loading and release characteristics,protein adsorption and hemolysis,cytotoxicity,and cellular uptake of the nanocarrier material were studied.The results are as follows:(1)FRET-CMS has a spherical morphology with a typical IV mesoporous structure.The relatively uniform size were about 90 nm.And they also have good stability in aqueous solution;The material has reductive susceptibility,the disulfide bond was cleaved at a high concentration of glutathione(GSH),the potential rapidly changes and the donor(RhB)and acceptor(Znq)of FRET are separated,resulting the red fluorescence at 571 nm gradually weakened and the green fluorescence at 495 nm gradually increased when excited at 380 nm,demonstrating that GSH can effectively control the FRET switch.(2)6-MP effectively loaded in mesoporous channel of FRET-CMS with drug loading and entrapment efficiency of 5.2~7.4%(w/w)and 34.2~41.4%(w/w),respectively.The in vivo release behavior of 6-MP@FRET-CMSin different pH and different concentrations of GSH solutions at 37? showed that the release were less than 10% under the conditions of low concentration of GSH and p H 7 PBS solution over a period of 24 h,when added 10 mM GSH,the release rate was as high as 81.3% over the same time,indicating a good redox-responsive property.(3)The biosafety results of FRET-CMS showed that HA on the surface of FRET-CMS could significantly reduce the non-specific protein adsorption,and without hemolysis in the concentration range of 20-1500 ?g/m;cell experiments showed that FRET-CMS has good biocompatibility within the range of a certain concentration,and 6-MP@FRET-CMS inhibited the activity of CD44 overexpressed HeLa cells more strongly than CD44 receptor-negative MCF-7 cells.The of dead cells and living cells consistented with the cytotoxicity experiments.The cellular uptake experiments of materials by Hela and MCF-7 cells showed that the enhanced uptake of FRET-CMS was attributed to HA-CD44 mediated endocytosis.In conclusion,the FRET-based redox-responsive mesoporous silica nanocarrier drug delivery system could integrate the targeted delivery,controlled release with real-time monitoring of drug release,making it a promising nanomaterial for drug delivery.