A targeting photodynamic drug vehicle composed of neural stem cells and mesoporous silica nanoparticles for tumor therapy / 中国组织工程研究

ABSTRACT

BACKGROUND:Neural stem cells (NSCs),which exert no promoting effect on tumor growth and break through the blood brain barrier to deliver drugs into tumor tissues,are considered as a promising tumor targeted drug delivery vehicle.OBJECTIVE:To develop a hybrid delivery system composed of NSCs and moseporous silica nanoparticles for photosensitizer delivery,and to test if the system can be used for tumor therapy.METHODS:The photosensitizer,zinc phthalocyanine,was encapsulated in mesoporous silica nanoparticles.(1) Cytophagy experimentNSCs were incubated with mesoporous silica nanoparticles (0,10,50,100,200 mg/L) loaded with zinc phthalocyanine for 6 hours,and fluorescence microscope was employed to observe the nanoparticles inside the cells.(2) Cytotoxicity testNSCs incubated with mesoporous silica nanoparticles at various concentrations (0,10,50,100,200 mg/L) which loaded with or without zinc phthalocyanine for 6 hours,followed by 3 days of normal culture.Then,the cells were harvested for MTT assay.(3) Retention of nanoparticles within the NSCs100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine were co-cultured with NSCs for 6 hours.Then,the cells were normally cultured for 12,24,and 72 hours,and observed with fluorescence microscope.(4) Zinc phthalocyanine excitation in vitro100 mg/L mesoporous silica nanoparticles loaded with or without zinc phthalocyanine were co-cultured with NSCs for 6 hours.The cells were then normally cultured for 12 hours and irradiated with laser.Microscope was employed to observe cell morphology.(5)Tumor cell killing experimentNSCs cells were cultured with 100 mg/L mesoporous silica nanoparticles loaded with zinc phthalocyanine,then mixed with MCF7 cells for 12 hours,and irradiated with laser.After that,the cells were cultured for another 12 hours and cell death was observed under fluorescence microscopy.RESULTS AND CONCLUSION:(1) After co-cultured with the calls for 6 hours,nanoparticies could be found in the cytoplasm and the number was increased with the concentration of nanoparticles.(2) The nanoparticles with or without zinc phthalocyanine loaded at the concentration of ＜ 100 mg/L showed no toxicity to NSCs.(3) After 72 hours of co-culture,the nanoparticles in the cytoplasm was decreased in number,but still could be found.(4) Laser irradiation could damage the cell membrane of NSCs co-cultured with mesoporous silica nanoparticles loaded with zinc phthalocyanine.(5) A large number of MCF7 cells died after tumor cells were co-cultured with NSCs that were cultured with mesoporous silica.To conclude,the hybrid system composed of NSCs and mesoporous silica nanoparticles loaded with zinc phthalocyanine can serve as a great potential tumor-targeted delivery vehicle for photodynamic therapy.