The research team of Shanghai Institute of medicine of Chinese Academy of Sciences develops "cocktail" delivery strategy to provide new ideas for effective improvement of breast cancer treatment

The incidence rate of breast cancer is the highest in female cancer patients Metastasis and recurrence are the main causes of death in breast cancer patients In recent years, the combination of chemotherapy and immunotherapy has become a research hotspot of cancer treatment, but tumor stem cells (CSC) are often tolerant to T cells, and the proportion of CSC in tumor tissue is low, and the targeting of chemotherapy drugs to CSC is poor In response to the above problems, Lang Tianqun, a doctoral candidate in the pharmaceutical preparation center of Shanghai Pharmaceutical Research Institute, Chinese Academy of Sciences, and other researchers, under the guidance of Yin Qi and Li Yaping, designed a "cocktail" delivery strategy: through the construction of spatiotemporal controllable nanoparticles (PM @ THL) To integrate chemotherapy for common tumor cells and tumor stem cells with immunocheckpoint blocking therapy PM @ THL has double structure of micelle liposome and double response of enzyme sensitivity and acid sensitivity It can effectively package paclitaxel, thiolidazine and hy19991, a small molecular inhibitor of PD-1 / PD-L1, for the treatment of metastatic breast cancer The results showed that the particle size of PM @ THL was about 100 nm, and it was not easy to be cleared by monocyte megaphagocyte system, and its pharmacokinetics was stable When it was delivered to tumor tissue, it was dissociated into micelles with particle size of about 40-50 nm, which was beneficial to be absorbed by tumor cells and achieved the purpose of time-space sequential release In the mice model of metastatic breast cancer, PM @ THL can effectively increase the drug concentration in tumor cells, the tumor inhibition rate is 93.45%, and the lung metastasis inhibition rate is 97.64% At the same time, the proportion of CSC in the tumor tissue of the mice in the test group decreased, the number of killer T cells infiltrated increased, the survival period of the animals significantly prolonged, and the tumor volume continued to decline after the end of the administration cycle This work provides a new idea for the prevention and treatment of breast cancer metastasis and recurrence The above research results were published in the international authoritative journal advanced materials (DOI: 10.1002 / ADMA 201806202) on the topic of "cocktail strategy based on spatio temporarily controlled nano device improvements therapy of breast cancer" The project is supported by key projects of NSFC, innovation group fund and youth innovation promotion association of Chinese Academy of Sciences.