| Traditional cancer therapy,(such as surgery,chemotherapy,radiotherapy and immunotherapy)has been widely applied for tumor inhibition.At present,the therapeutic effect of traditional treatment is significantly limited by tumor specificity,serious side effects and drug resistance.In the consideration of diversity,complexity and heterogeneity of tumor,the cancer-specific treatment urgently needed.In this study,graphene supported tetravalent zirconium tetravalent porphyrin(AGO/PCN-224)was designed with a combining effect of photodynamic and photothermal therapy,which was further supposed to achieve bifunctional inhibition of the tumor growth as a result.(1)Synthesis and characterization of materials.Using amine modified graphene oxide(AGO)as the carrier,zirconium chloride,benzoic acid and mesoporphin(4-carboxyphenyl)porphin were added.Through the highpressure hydrothermal reaction process,the AGO/PCN-224 nanomaterial with the particle size of about 200 nm was synthesized.Zeta potential was29.66 mV,which showed the best dispersion.The results of XRD,Fourier infrared spectrum and UV-vis spectrum also confirm the successful preparation of the above materials.Photothermal imaging experiments characterized the photothermal effects of AGO/PCN-224 and AGO/PCN-224 in vitro.The results showed that AGO/PCN-224 has good photothermal effects,and the temperature reached 50.9 ℃ in 5 min.(2)Anti-tumor study in vitro.In the phototoxicity experiment,mouse triple negative breast cancer cells(4T1 cells)were adopted as tumor cells.The cells were incubated in the presence of nanomedicines for 4 h and subsequently treated with near infrared laser for another 5 min.The cell survival rate was detected by chemiluminescence method.The optimal cell death rate reached 70% by using 15 μg/mL of AGO/PCN-224.In the comparative experiment of ROS yield in vitro,the ROS yield of AGO/PCN-224 at 5,15 and 25 μg/mL was 36.8%,79.3% and 83.5% respectively,which was obviously higher than PCN-224 at the same concentration.The results of apoptosis experiment show that the proportion of apoptosis treated with AGO/PCN-224 was 61.6%,which was significantly higher than AGO(19.66%)and of PCN-224(23.91%).The results of inverted fluorescence microscope compared with living/dead cells show that AGO/PCN-224 has a good performance on inhibiting the growth of tumor cells.At the cellular level,AGO/PCN-224 has an excellent ability to produce reactive oxygen species and inhibit the growth of tumor cells.(3)Anti-tumor experiment in vivo.The mouse strain Balb/c was inoculated with 4T1 cells in the armpit.The dose of AGO,PCN-224 or AGO/PCN-224 nanomaterials was 5 mg/kg,once every three day.And then,the mice were treated with near-infrared laser irradiation on the tumor site for 5 min.AGO/PCN-224 exhibited good photothermal effect in mice,and the temperature of tumor site reached 51 ℃ after 5 min illumination.After periodic illumination and the treatment of nanomaterials,the tumor growth of AGO/PCN-224 group was significantly inhibited.Finally,the average tumor mass of AGO/PCN-224 group was 0.199 g,0.980 g,and 0.481 g,respectively.The result of paraffin section and HE staining suggest that AGO/PCN-224 nanomaterials has no obvious biological toxicity towards the main organs of mice. |
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