Tumor Combined Immunotherapy Based On Super Virus Composite Nanomaterials

Traditional cancer treatment methods such as surgery,chemotherapy and radiation therapy have greatly reduced the mortality rate of cancer.However,these treatment methods bring a great burden to the body,and after the malignant tumor has metastasized,it is difficult for the above-mentioned traditional methods to completely cure the cancer.Immunotherapy of tumors can improve the anti-tumor immune response.The emergence of immunotherapy changes the way of treating tumors and provides hope for tumor treatment.However,current immunotherapy still has drawbacks such as relapse and metastasis.Viruses can activate cellular and humoral immunity,especially cellular immunity,which can bring new directions for cancer treatment.This study uses non-pathogenic Sendai virus(SEV)as a common virus to activate the immune system to wake up the innate and adaptive immune system in the body by recruiting and activating a large number of macrophages,dendritic cells,and cytotoxic T lymphocytes After these immune cells mature,they can secrete a large amount of anti-tumor cytokines to promote the immune cells to kill the tumor,thereby inhibiting the growth and reproduction of tumor cells.We designed two superviral nanocomposites.First,we used an anti-CD47 antibody(a CD47)to prevent the interaction of the CD47 molecule on the cell surface with its receptor signal-regulating protein α(SIRPα),using biocompatible polymer Lactic acid-glycolic acid-bpolyethylene glycol(PLGA-PEG)is used as a carrier to assemble Sendai virus,and a CD47 serves as a release library for immunomodulators;N,N’-((6,7-diphenyl-[1,2,5]thiadiazolo[3,4-g]quinoxaline-4,9-diyl)bis(4,1-phenylene))bis(Nphenylnaphthalen-1-amine)(TQ-BPN),which has an aggregation-induced emission(AIE)effect in the infrared region to track immunotherapeutics in real time and finally form(SEV + a CD47)@PLGA nano virus complex,in which complex,TQ-BPN molecule can be used as observation nano Molecular probes for particle integrity to indicate the release of SEV and a CD47 extracellularly in vivo.SEV can effectively recruit and activate innate immune cells,such as macrophages and dendritic cells,enhance phagocytosis and antigen presentation against tumors.At the same time,these natural viruses can also effectively stimulate the immune system to produce a large number of cytokines(TNF-α,IFN-γ,IL-6)to promote immune cells to kill tumors and inhibit the growth and reproduction of tumor cells.Subsequently,the viral nanocomposites gradually release a CD47 encapsulated in the tumor area,thereby blocking the interaction of CD47 and SIRPα,and promoting the phagocytosis of macrophages against tumor cells,thereby enhancing the anti-tumor T cell response.Our research shows that this synergistic immunotherapy based on the activation of the whole body immune system by natural viruses and the prevention of tumor escape through a CD47 can kill cancer cells to the greatest extent.Second,we studied another superviral nanocomposite composed of SEV a \ ICG b \ Ca HPO4 c.In this system,Ca2+ can induce tumor cell apoptosis,and the light and heat combined with ICG and NIR kill the tumor and release it.A large number of tumor antigens,these released antigens are presented to T lymphocytes by the antigen-presenting cells(APC)recruited and activated by SEV to induce their maturation and destroy the tumor cells,producing a large number of anti-tumor cytokines,and then awakening the systemic anti-tumor immune response.Our research shows that this superviral nanocomposite triggers the systemic immune system to maximize the killing of tumor cells and inhibit in situ tumor recurrence and potential metastatic spread.All in all,our research proposes two new cancer treatment strategies,both of which can eliminate primary tumors,attack and kill spreading metastatic tumors,and generate immune memory to prevent tumor recurrence.These two super virus nanosystems are simple to prepare and have significant anti-tumor effects.They provide a solid foundation for designing novel tumor treatment schemes and synergistic immunotherapy,and have good application potential in future clinical research.