| Objectives: Cancer is the main cause of death every year,and it is still a serious disease worldwide.Among all types of skin cancer,melanoma is the most aggressive malignant tumor.Because of its unique physical properties such as high tissue permeability,colloidal stability and relatively low cost,nanoparticles have made great strides in the field of medical research,especially in cancer treatment."Green chemistry" is widely used in the field of nanoscience due to its advantages of environmental protection,energy saving and low cost,and is often used in the synthesis of gold nanoparticles.In this study,green tea extract(GT)was used to generate gold nanoclusters under mild conditions for cancer treatment for the first time.Methods: In this experiment,we prepared doxorubicin(DOX)loaded gold nanoclusters(Au-GT-DOX)by using green tea extract,to realize the combination of photothermal therapy and chemotherapy for melanoma.Tea polyphenols in green tea were extracted by hot water with the method of "green tea chemistry",the components of green tea extract were analyzed by high performance liquid chromatography.Chloroauric acid was reduced by green tea extract to form gold nanoclusters,and DOX was entrapped into the green synthesized gold nanoclusters.The particle size and zeta potential of the nanoclusters were measured by dynamic light scattering,and the morphology of them was observed by transmission electron microscope.In vitro photothermal effects of Au-GT-DOX were investigated by irradiating the nanoclusters with 808 nm near infrared light.Au-GT-DOX was incubated with B16F10 cells to investigate the uptake of nanoclusters by tumor cells and the in vitro anti-tumor effect.The in vivo photothermal effect with 808 nm near infrared light and the in vivo anti-tumor effect of Au-GT-DOX were investigated on melanoma bearing C57BL/6 mouse model.Results: The preparation conditions of green tea extract and nanoclusters were mild,the reaction was rapid,the materials were environmentally friendly,and the raw materials were cheap,which fully reflected the principle of "green chemistry".Chloroauric acid was reduced by green tea extract to form gold nanoclusters.DOX is entrapped into the green synthesized gold nanoclusters by ?-? stacking and electrostatic interaction with green tea extracts.Simultaneously,in the oxidative polymerization process of GT,DOX could co-polymerize with polyphenols and be efficiently entrapped in the nanoclusters through ?-? stacking and electrostatic interactions.In this drug delivery system,GT acted as a reducing agent of HAuCl4,stabilizer of nanoclusters and provided a co-polymerization site for DOX.And the resulting polyphenols oxide can assemble into oligomer to constrained gold nanoparticle,making it stable nanoclusters.Au-GT-DOX nanoclusters had uniform particle size and good stability.It could increase the temperature rapidly with near infrared irradiation in vitro and had good photothermal stability.The drug delivery system could promote the uptake of DOX by B16F10 and could effectively kill B16F10 cells in vitro.The temperature of the tumor area of melanoma bearing C57BL/6 mice rose rapidly in vivo,when the Au-GT-DOX was injected.The result of in vivo anti-tumor experiment on melanoma bearing C57BL/6 mice showed that combined chemotherapeutic effect of DOX with hyperthermia effect of gold could effectively inhibit the growth of tumors,prevent the recurrence of tumors,and even completely eliminate tumors.Conclusions: Au-GT-DOX was a promising drug delivery system with three outstanding advantages:(1)Both the extraction process of tea polyphenols and the synthesis process of gold nanoclusters followed the principle of "green chemistry",without introducing any organic solvents,the reaction conditions were mild and fast,the whole process is energy-saving and environmentally friendly,and the carrier was biologically safe and biocompatible.(2)Chemotherapy combined with photothermal therapy could improve the therapeutic effect of cancer and reduce systemic toxicity and side effects by combing different kinds of treatments in a single drug delivery system.(3)The drug delivery system had a good therapeutic effect on tumors.In vivo anti-tumour experiments showed that the drug delivery system could effectively inhibit the growth and recurrence of tumors,and even completely eliminated tumors.The construction of the drug delivery system provided a new idea for the construction of drug delivery system with green tea extract for cancer therapy. |
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