Construction Of Three-dimensional Supramolecular Organic Frameworks Drug Delivery System And Study Of Treating Multidrug Resistance In Breast Cancer

Background According to the survey results of the World Cancer Center,by 2020,breast cancer has surpassed lung cancer（11.7%）,becoming the most common cancer.Currently,chemotherapy is still one of the principal methods of clinical treatment of breast cancer,with good curative effect.However,the long-term use of chemotherapeutic drugs causes breast cancer cells to develop drug resistance.The drug resistance of breast cancer cells has become the primary cause of failure and recurrence of breast cancer chemotherapy.Many studies have shown that nano-drug delivery system could reverse drug resistance to a certain extent.Purpose We use supramolecular self-assembly technology to construct a pH-responsive three-dimensional supramolecular organic frameworks nano-drug delivery system（SOF@DOX）to achieve the purpose of pH response and passive targeting and overcoming breast cancer resistance.Method The characterization of SOF by energy dispersive X-ray spectrometer,dynamic light scattering instrument,transmission electron microscope,small-angle X-ray scattering instrument,etc.The anti-tumor effect of SOF@DOX on MCF-7/ADR in vitro was evaluate through experiments such as cytotoxicity,cell uptake,and apoptosis.The tumor model of nude mice bearing MCF-7/ADR cells was constructed by injecting MCF-7/ADR cells into the right axilla of BABL/c nude mice.The anti-tumor effect of SOF@DOX on MCF-7/ADR in vivo was evaluate through taking the results of tumor volume,tumor weight,and tumor inhibition rate as indicators.Result The particle size of SOF is 135±28nm and the structure of SOF is similar to the network structure of diamond topology.SOF has crystallinity and porosity and can maintain periodic order in both the solid phase and the solution phase and has a high degree of stability.The drug loading of SOF@DOX was 5.12%±0.14.The encapsulation rate of SOF@DOX was 81.92%±2.2.Within 72hours,about 80%,45%,and 15%of DOX are released from SOF@DOX in the PBS of pH=4.8,pH=5.6,and pH=7.4,indicating that SOF@DOX have pH-responsive drug release characteristics.The uptake rate of SOF@DOX by MCF-7/ADR cells was significantly higher than that of free DOX and SOF@DOX could be effectively taken up by MCF-7/ADR cells.The IC₅₀ values of free DOX and SOF@DOX for MCF-7/ADR cells were 30.48μg/m L and 7.724μg/m L（approximately 4 times）,The IC₅₀ values of free DOX and SOF@DOX for MCF-7 cells were 6.044μg/m L and 4.360μg/m L.SOF@DOX could enhance the sensitivity of MCF-7/ADR cells to DOX and could significantly induce apoptosis of MCF-7/ADR cells.Only the DOX group of nude mice lost weight,and the nude mice showed slowness and shortness of breath after DOX injection,indicating that SOF@DOX have low toxicity to nude mice in vivo.taking the results of tumor volume,tumor weight,and tumor inhibition rate as indicators,shows that SOF@DOX can significantly inhibit tumor growth.The organs tissue sections of SOF group and SOF@DOX group had no pathological features such as injury,necrosis or fibrosis,indicating that both SOF and SOF@DOX have good histocompatibility and no serious adverse reactions to the organs of nude mice.The tumor tissue of the control group and the SOF group shave no obvious damage and apoptosis.The tumor tissues of the DOX group have certain damage and apoptosis,the tumor tissues of the SOF@DOX group showed obvious damage and a large number of cell apoptosis.indicating that the SOF@DOX group has the best therapeutic effect.Conclusion We successfully constructed a new type of three-dimensional supramolecular framework nano drug delivery system（SOF@DOX）and completed the corresponding evaluation,achieving the goal of overcoming breast cancer drug resistance.The three-dimensional supramolecular framework nano drug delivery system（SOF@DOX）has outstanding performance such as passive targeting,pH-responsive drug release,and overcoming breast cancer resistance.As a new type of supramolecular nano-medicine carrier,three-dimensional supramolecular framework material may have a good prospect in the delivery of anti-tumor drugs and the treatment of drug-resistant breast cancer.This subject provides new ideas for the design and development of new drug delivery systems,and provides a theoretical basis and experimental basis for treating drug-resistant breast cancer.