Construction Of A Temporal Drug Delivery System For Injectable Silk Protein Hydrogels And It’s Application In Tumor Immunotherapy

Immunotherapy has made important breakthroughs in the clinical management of a variety of advanced malignancies.However,most patients do not benefit from the currently available immunotherapies and experience immune-related adverse effects such as high drug side effects and cytokine storms.In this thesis,an injectable composite hydrogel capable of the temporal release of the loaded drug was prepared for immunotherapy of tumors by loading oxaliplatin,a chemotherapeutic drug that mediates immunogenic apoptosis,and biodegradable nanocapsules encapsulated with an anti-PD-L1 monoclonal antibody,an immune checkpoint inhibitor,using natural silk protein as the matrix material.During treatment,oxaliplatin is rapidly released at the tumor site,killing tumor cells,triggering immunogenic apoptosis,releasing tumor-associated antigens,stimulating the body’s immune response,and improving immune response responsiveness.As the nanocapsules degrade,the anti-PD-L1 monoclonal antibody is continuously released and retained at the tumor site for a prolonged period,improving the efficacy of immune checkpoint blockade therapies.In this thesis,an injectable silk protein hydrogel drug delivery system was constructed to reverse the tumor immunosuppressive microenvironment,prolong the duration of action of immunotherapy and ultimately inhibit tumor growth effectively through the controlled chronological release of oxaliplatin and anti-PD-L1 monoclonal antibody in synergy with immunogenic apoptosis and immune checkpoint blockade.