Exploration Of Novel Strategies For Triple-negative Breast Cancer Treatment And Prevention Based On Nanomaterials

According to the 2020 global cancer burden data released by the International agency for research on cancer,the number of new cases of breast cancer reached 2.26 million,surpassing lung cancer to become the cancer with the most new cancer cases in the world.In the long struggle against breast cancer,mankind has made a series of major breakthroughs.Current treatments can cure most types of breast cancer,but triple negative breast cancer is still difficult to treat.In recent years,new therapeutic strategies such as targeted therapy and immunotherapy for triple-negative breast cancer has been studied extensively,especially the anticancer strategy based on nanomaterials has been widely used in triple negative breast cancer.However,there are scanty anti breast cancer drugs that can be applied to clinical practice.The main reason is the potential safety risks of nano drugs.And the preparation process of most nano drugs is complex,which is difficult to achieve large-scale production.Therefore,there are still great challenges in the research and development of breast cancer nano-drugs with good biosafety,definite effect and simple preparation.Taking triple-negative breast cancer as a disease model,this paper explores new strategies for the treatment and prevention of triple-negative breast cancer based on nanomaterials.The main research contents are as follows:Chapter 1:Briefly describes the research progress of breast cancer treatment,focusing on the research background,basis of topic selection and significance of this paper.Chapter 2:Amorphous calcium carbonate-doxorubicin complex(ACC-DOX)with pH sensitivity and rapid drug release was synthesized in situ based on hollow Fe3O4 nanoparticles,and then it was modified with hydrophobic oleic acid to protect ACC-DOX from dissolution and release in advance when circulating in vivo.Finally,PEG/Fe3O4-ACC-DOX was obtained by surface modification with polyethylene glycol.After intravenous administration,PEG/Fe3O4-ACC-DOX can reach around the tumor vessels due to the high permeability and retention effect of the solid tumor.Then,PEG/Fe3O4-ACC-DOX can be magnetically assembled in a magnetic field to increase the particle size and enhance its retention in solid tumors.In vivo test results show that PEG/Fe3O4-ACC-DOX has good tumor accumulation and retention ability under the action of external magnetic field,and has good antitumor effect.Chapter 3:An injectable live cell cancer vaccine(InLCCV)with near-infrared laser(NIR)activation properties was constructed based on gold nanorods(GNRs).It is prepared by simply mixing gold nanorods(GNRs),mouse breast cancer cells(4T1)and ultra-low dose lipopolysaccharide(LPS)with thermosensitive hydrogel matrix(F127).After subcutaneous injection,due to the temperature response of F127,the in situ gel can be rapidly formed under the skin.Under the irradiation of near-infrared laser,immunogenic cell death(ICD)of 4T1 cells was induced by in situ low heat using the photothermal effect of GNRs.Subsequently,a large number of breast cancer associated antigens were released to the surrounding environment.Dendritic cells and macrophages were activated correspondingly.Low dose LPS as an immunomodulator further enhanced the immune response,eventually leading to systemic anti-tumor immune response.After inoculating InLCCV,the tumor-free rate of mice was 60%,and the survival rate was as high as 80%during the observation period.The results of lung metastasis test showed that the number of pulmonary metastatic nodules in the control group was 3.9 times higher than that in the InLCCV group.In addition,InLCCV also showed inhibitory effect on orthotopic tumors.In conclusion,a novel nano-drug delivery platform that can be magnetically assembled under the action of an external magnetic field and a near-infrared light-triggered injectable live-cell breast cancer vaccine are developed based on nanomaterials.Taking triple-negative breast cancer as a disease model,we systematically studied the role of two new strategies in the prevention and treatment of triple-negative breast cancer,which provided a new scheme and strategy for clinical prevention and treatment of triple-negative breast cancer.