The research group of Professor Shi Shuo of Tongji University has constructed a multifunctional nano anti-tumor drug complex

Breast cancer has been the leading cause of malignancy worldwide The incidence rate of recurrence and metastasis of three negative breast cancer (TNBC) is high The survival time of patients with recurrence and metastasis is short and the prognosis is poor Chemotherapy is easy to be drug-resistant At present, the main treatment methods of TNBC are surgical resection, chemotherapy and radiotherapy It is impossible to target estrogen and progesterone receptor antagonists and HER-2 Therefore, how to improve the therapeutic effect of TNBC is a difficult problem in clinical breast cancer treatment To solve this problem, Professor Shi Shuo's research group of School of chemical science and engineering of Tongji University and Professor Dong Chunyan, director of breast cancer Department of Oriental Hospital Affiliated to Tongji University carried out interdisciplinary cooperative research, and proposed a new strategy of chemotherapy combined with immunotherapy combined with photothermal and photodynamic technology in the treatment of TNBC Recently, relevant research results were published on advanced materials (DOI: 10.1002 / ADMA 201904997) In recent years, with the launch of ipilimumab and nivolumna, immunotherapy has made revolutionary achievements in the field of tumor therapy by activating maladjusted or depleted cytotoxic T cells (CTLs) to identify and kill tumor cells Although immunotherapy has achieved good results in melanoma and non-small cell lung cancer (NSCLC), the effect is not so significant in breast cancer treatment The less infiltration of CTLs and the more load of MDSCs are the main factors MDSCs can reduce the proliferation of T cells and promote the apoptosis of CD8 + T cells, leading to immunosuppression MDSCs can be divided into two types, M1 and M2 M1 can secrete IL-12 and TNF - α to kill tumor cells, while M2 is usually called tumor related macrophages, which secrete IL-10, IL-4 and IL-13 to promote tumor angiogenesis The traditional view is that chemotherapy can inhibit the immune system, but the latest research shows that low-dose chemotherapy drugs can promote tumor immunogenic death or participate in tumor specific immune response, such as docetaxel (DTX) can promote the transformation of MDSCs from m2 to M1 CPG, as an immune adjuvant, can specifically recognize toll like receptor 9 on the surface of plasma like antigen presenting cells, and then stimulate type 1 T cell helper cells (Th1) to produce proinflammatory factors (such as TNF - α, IL-12) As the most effective stimulant, IL-12 can induce a large number of CTLs to infiltrate the tumor site, and the activated CTLs secrete IFN - γ to kill tumor cells Therefore, Professor Shi Shuo and Professor Dong Chunyan carried out interdisciplinary cooperative research and actively tried to treat TNBC through chemotherapy combined with immunotherapy The researchers used copper sulfide (CUS) as a drug carrier loaded with low dose docetaxel to provide photothermal therapy The active targeting of tumor receptor folic acid (FA) was used to make nanoparticles effectively target tumor focus At the same time, in order to improve the water solubility of nanoparticles and realize the loading of CPG, the researchers coated the surface of CuS with polyethyleneimine protoporphyrin IX (PEI PpIX), which helped CpG adsorb on the surface of nanoparticles and achieve photodynamic therapy Finally, a multifunctional nano anti-tumor drug complex fa-cus / DTX @ Pei PpIX CpG (FA-Cd @ PP CPG) was constructed After intravenous injection, FA-Cd @ PP CPG can be targeted to the tumor site, and DTX and CPG are released DTX promotes M2 subtype of MDSCs to transform into M1 subtype and secretes IL-12 and TNF - α, while CpG recognizes antigen presenting cells, and promotes Th1 cells to produce IL-12 and TNF - α Increased IL-12 can promote T cells to infiltrate into the tumor site and activate CTLs activated by CTLs IFN - γ is secreted to kill tumor cells After T cells infiltrate into tumor site, PD-L1 antibody (apd-l1) is injected subcutaneously to further enhance the effect of immunotherapy, so as to achieve the goal of systemic therapy This is a new strategy of chemotherapy combined with immunotherapy, local therapy combined with systemic therapy Zhou Lulu, a direct doctoral student, and Chen LV, a master's student, are the co first authors of this paper Professor Shi Shuo and Professor Dong Chunyan, an Oriental Hospital Affiliated to Tongji University are the co correspondents of this paper.