Sono-Immunotherapy Based Liposomes For The Treatment Of Malignant Tumors

Cancer poses a serious threat to human life and health.The clinical treatment of cancer at this stage mainly includes surgery,chemotherapy,and radiotherapy.Although these therapies have achieved significant therapeutic effects,they also have certain adverse reactions.Not only are the therapeutic effects limited,but they are also prone to a great burden on the body and it is difficult to cure after metastasis.Based on the shortcomings mentioned above,it is vital that we find a new treatment method to meet the needs of targeted killing of cancer cells while inhibiting tumor metastasis and recurrence.Sonodynamic therapy(SDT)has the characteristics of high tissue penetration,non-ionizing properties,high controllability and low cost,especially for the treatment of deep tumors.In classic sonodynamic therapy(SDT),ultrasound activates a sonosensitizer to produce reactive oxygen species(ROS),which leads to the death of cancer cells through apoptosis or necrosis.It is reported in the literature that the tumor cell fragments killed by sonodynamic can be used as tumor antigens to be captured by the dendritic cells and cause anti-tumor immunity.However,experiments have shown that the immune response caused by sonodynamic therapy is not sufficient to effectively inhibit tumor growth and metastasis.Mainly because dendritic cells are in an immunosuppressive microenvironment,the ability of dendritic cells to present antigens is limited.On the other hand,the production of ROS depends on oxygen.However,solid tumors are in a hypoxic state,and with the tumor progression and the increase of malignancy,the hypoxic state will aggravate,which will restrict the production of reactive oxygen species(ROS)under hypoxic conditions.Based on the above,we constructed a liposome co-loaded with sonosensitizers,cinnamaldehyde derivatives and immune adjuvants.It can overcome the low efficiency of sonodynamic therapy caused by tumor hypoxic environment and enhance the killing effect of SDT on tumor in situ.At the same time,through the combination of immunotherapy and SDT can activate the body’s anti-tumor immune response to prevent tumor metastasis.This paper is divided into three parts: preparation and characterization of liposomes,in vitro anti-tumor activity research,and treatment effect research of mouse orthotopic breast cancer lung metastasis model.It mainly evaluates the killing effect of sonodynamic combined immunotherapy on orthotopic tumor cells and inhibit the occurrence of metastases.This study used liposome nanocarriers with high biosafety to enrich chlorin e6 trimethyl ester,cinnamaldehyde derivatives,and MPLA in breast cancer,and activated the chlorin e6 trimethyl ester to kill tumors by ultrasound.At the same time cinnamaldehyde derivatives act on mitochondria to break the balance of oxidative stress and further enhance the production of ROS.MPLA in the lipid outer layer acts as a TLR4 agonist,which can enhance the maturation of dendritic cells and the secretion of cytokines to induce immune response and kill tumor cells.This study aims to enhance the anti-tumor effect of SDT,prevent tumor metastasis,solve the problems existing in traditional tumor treatment methods,and provide new ideas for anti-tumor treatment.