Constructionof PH Responsivecore-shell Magnetic Mesoporous Silica Nanocomposites Andits Applicationin Photodynamic Therapy

Core-shell magnetic mesoporous silica nanocomposites are a kind of nanocomposites which make magnetic nanoparticle as the core and mesoporous silica as the shell.With respective characteristics of magnetic nanoparticle and mesoporous silica material such as magnetic targeting,large surface area and easily modified inner surface,the core-shell magnetic mesoporous silica nanomaterials are both overcome the defects of easy agglomeration and oxidation for the magnetic nanoparticle,which make them have the good application in the research filed of biomedicine,environment,chemistry,and so on.Photodynamic Therapy(PDT)emerged in 1970 s,mainly to use the photosensitizer stimulatingbyspecific wavelength produce singlet oxygen tokill tumor cells.PDT has great application prospect in treating melanoma,breast cancer andother superficial tumors,also it shows certain effect in anti-infection of virus by HPV such as treatment of vulvar/vaginal condyloma,and photosensitizers are thehot research of new anti-tumor drugs at present.However,there are still some problems in PDT.On one hand,patients in the treatment process,need to avoid the light from beginning to end,otherwise it will cause serious systemic toxic side effects which limits itsapplication.On the other hand,the distribution of photosensitizers in vivo lacks the clear tumor targeting mechanism,and their effective concentration in tumor site is not high,whichaffectthe efficiency of PDT and cause side effects.Aiming at the main problems in PDT,the responsive nanoparticle drug delivery system are synthesized,which could effectively target the photosensitizer to tumor site by modern nanotechnology,to achieve effective photosensitizer targeting on the tumor site,responsive release in the local tumor part,and effectively improve the drug concentration in the tumor tissue,reduce systemic side effects.First of all,a core-shell magnetic Fe3O4 mesoporous silica nanocomposites(MMSN)were designed and synthesized,and depended on the superparamagnetic Fe3O4 mesoporous silica nanoparticles(MMSN)to load the model photosensitizer rose bengal(RB)and functional modified a block polymer polyethylene glycol-b-poly aspartic acid(PEG-b-PAsp)in the surface of mesoporous silica to form the final pH responsive core-shell magnetic mesoporous silica nanocomposites(RB-MMSNs),and made the related characterizations.By the transmission electron microscope,MMSN revealed good spherical morphology,good mesoporous properties and the average diameter was ~190nm.Through the modification of PEG-b-PAsp on the surface of mesoporous silicon,the RB-MMSNs had a certain pH response,and found that it could also increase the coverage rate of RB on the mesoporous silicon layer,making the RB loading rate up to 36%.The magnetic saturation intensity was about 26.6emu/g,and the relaxation rate was close to 52.52S-1mM-1,reflecting good effect of the magnetic target,and could be used in magnetic resonance imaging.Then in vitro experiment,the nanocomposites(RB-MMSNs)were not have obvious toxicity in dark,could been significantly taken up by mouse melanoma cell(B16)comparing to free RB and even much higher on the magnet field.With the irradiation of LED green light for 3min,the half inhibition rate of cell was close to 4.85μg/mL,while it was high to 48.86μg/mL for free RB.Both the results of CCK-8 and flow cell apoptosis detection showed that the cell killing capability of RB-MMSNs was 10 times than free RB at the same RB concentrations.Thus,RB-MMSNs greatly improved the efficiency of PDT on B16 cells in vitro.Finally,in order to further text the function of PDT,the animal experimentswere made.Magnetic resonance image(MRI)and Prussian blue staining results expressed the perfectly physical target in tumor site.Owning to the strong magnetic targeting of RB-MMSNs,there was a significantly smallest tumor size by the therapy method of magnetic field induced and the light irradiation.At the same time,the survival time in the group was relative longer than other groups.The results of TUNEL assay also proved that the RB-MMSNs had good therapeutic effect in vivo.In short,RB-MMSNs with high transport efficiency of photosensitizers,obvious magnetic targeting,pH response release characteristics in vitro and in vivo,low biodegradation rates and side effects were synthesized,which largely solvedthe problems,such as the effective concentration of the most photosensitizerswere not highin tumor tissue part,easy to leak in the transport process that resulting the problems of side effects and were expected to become a set of magnetic targeting and pH response of multifunctional nanocarrier to enhance the effect of PDT on clinical tumor therapy.