The Co-delivery Of 5-FU And TRAIL Plasmid By Functionalized Dendrimer In The Treatment Of Bone Metastasis Of Breast Cancer

Background and objective:As a kind of common malignant tumor,breast cancer is often associated with factors such as heredity,age and hormone levels,and 99% in women,the incidence of the disease accounted for about 15% of all of the tumors,and therefore it is a serious threat to the health of women.At present,the principal treatment of breast cancer is the comprehensive treatment including surgical resection.With the abundance of the comprehensive treatment in patients with advanced breast cancer,the incidence of bone metastases is about 70%,postoperative regular medical treatment is also required in breast cancer patients with bone metastasis.However,a growing number of molecular biology and cell biology researches have shown that the inherent specificity and complexity in breast cancer cells may make it harder for simple chemotherapy after surgery to achieve a radical cure thoroughly.Multi-drug resistance(MDR)of tumor cells in the treatment of cancer is a great scientific challenge.In recent 10 years,as a newly developed carrier,dendrimer has been more and more used in biomedical field because of its special structures.More and more researchers consider dendrimer materials as drug or gene carrier.We try to fabricate efficient,safe and controlled vectors for simultaneously drug and gene delivery in kill the MDA-MB-231 cell.Methods:In our research,we propose a versatile and ultraviolet light-responsive nano-carrier based on coumarin modified low-generation dendrimers to co-deliver 5-fluorouracil and TRAIL in the treatment of breast cancer,steps are as followed:(1)Connect the coumarin to low generation dendrimer G1 by the method of chemical modification to form a dendrimer-coumarin complex;Characterize of the complex and its related compounds;Evaluate the ability of the complex to delivery 5-fluorouracil,as well as the response to ultraviolet light;Evaluate the transfection efficiency of the complex with the response to ultraviolet light;Evaluate the transfection efficiency of the complex with 5 – fluorouracil?(2)Explore the relative proper quantity of dendrimer-coumarin complex as a carrier in TRAIL gene transfection in breast cancer cells;Explore the proper concentration of 5-fluorouracil in ultraviolet optical conditions,and study the inhibitory effect in breast cancer cells;Study the synergistic effect under the condition of ultraviolet optical as 5-fluorouracil and TRAIL gene carrier in inhibition effect of the treatment to breast cancer cells.Results:Dendrimer-coumarin complex can form proper nanoparticles by the methodof chemical modification;Transmission electron microscope,dynamic light scattering,one-dimensional MRI confirm the presence of nanoparticles;Ultraviolet light can control the load and release of 5 – fluorouracil;Ultraviolet light and 5-fluorouracil fail to affect complex in cell transfection efficiency;(2)Find out the most relatively suitable amount of complex as carrier,realize the optimal drug loading and unloading of 5-fluorouracil to inhibit cell concentration with the carrier in ultraviolet light conditions respectively;5-fluorouracil and TRAIL gene can inhibit breast cancer cells together,at the same time,we can control the load of 5-fluorouracil and release,implementation of 5-fluorouracil on-demand regulation with the ultraviolet optical carrier.Conclusion:Combination therapy of chemotherapeutics and gene therapy is an effective solution to multi-drug resistance,we fabricate the light-responsive multifunctional nanocarriers to prove their feasibility in synergistic treatment of breast cancer in vitro,which provide insight into the designing of dendrimer-based multifunctional nanocarriers for synergistic therapy of bone metastasis from breast cancer.