Aggregation-induced Emission Probe And Manganese Dioxide Nano-vaccine For The Diagnosis And Treatment Of Tumors

How to achieve efficient diagnosis and therapy of cancer is a serious problem in the world.With the development of nanobiomedicine,many researchers focus on aggregation-induced emission probes for cancer diagnosis and fluorescence image-guided cancer surgery,as well as inorganic nanoadjuvant vaccines.However,due to the lack of characteristics about targeted self-assembly in tumor,conventional aggregation-induced emission probes are difficult to achieve ideal effect of surgical resection.Meantime,most inorganic nano-vaccines lack the comprehension of the role in immune system,which affects their effects of immunotherapy.In order to improve the level of diagnosis and treatment in malignant tumor,we fabricated a new targeting of fluorescence probe MPA-Ph-R-FFGYSAYPDSVPMMS（MPA-Ph-R-FFGYS）with aggregation-induced emission.The probe consisted of three parts,including a new near-infrared aggregation-induced emission agent（MPA-Ph-R）,a self-assembling peptide（FFG）and a targeting peptide YSA（YSAYPDSVPMMS）.We evaluated the AIE properties and the selective targeting ability of MPA-Ph-R-FFGYSA towards 4T1 breast cancer cells overexpressing EphA2 protein in vitro.And then we established a peritoneal carcinomatosis-bearing model to evaluated the accuracy of tumor tissue diagnosis and the feasibility of guided surgical resection after MPA-Ph-R-FFGYSA intravenous injection in vivo.The results showed that MPA-Ph-R-FFGYSA had higher fluorescence brightness and sensitivity in the imaging of EphA2 clusters in vitro/vivo,and achieved accurate surgical resection of tumors.In order to achieve efficient immunotherapy of malignant tumor,we synthesized a novel manganese dioxide inorganic nanoparticles vaccine（MnO₂@OVA）by ovalbumin biomimetic method.In vitro,we performed characterization of MnO₂@OVA nanoparticles,and then evaluated endocytosis and immune activation of bone marrow-derived dendritic cells.In vivo,we studied the migration and immune stimulation effect of MnO₂@OVA nanoparticles in lymph nodes,and then assessed antitumor effect and antitumor immune response mechanism of MnO₂@OVA nanoparticles in tumor-bearing mice.The results showed that the size of MnO₂@OVA nanoparticles was about 50 nm.After being taken up by BMDC,MnO₂@OVA nanoparticles activateed c GAS-STING signaling pathway to induce high expression of costimulatory molecules（CD80,CD86）and antigen presenting molecule（MHCI）in BMDC in vitro.And MnO₂@OVA nanoparticles migrated to the lymph nodes and significantly stimulated the activation of dendritic cells and the secretion of IFN-γin CD8 T cells in vivo.Besides,whether MnO₂@OVA nanoparticles were served as prophylactic or therapeutic vaccines,they induced a strong immune response to inhibit tumor growth.In the study,a new aggregation-induced emission probe（MPA-Ph-R-FFGYSA）and new inorganic nano-vaccine（MnO₂@OVA）were expected to play prominent roles in the diagnosis and treatment of malignant tumor.On one hand,it provided a new strategy for the assembly orderly of aggregation-induced emission probes to enhance imaging detection and surgical treatment of cancer.On the other hand,it further enriched the inorganic nano-adjuvant library,and provided a reference for the future antitumor immunotherapy research of other new inorganic nano-vaccines.