Nanoparticle Enhanced Radiotherapy to Trigger Pyrolysis and Anti-Tumor Immunity

PURPOSE/OBJECTIVE(S) Clinical evidence demonstrated that combination of radiotherapy and immunotherapy may be more effective than either treatment alone. However, the efficacy of combined treatment was limited due to the low response rate of immune checkpoints inhibit (ICIs). Pyrolysis is a lytic proinflammatory cell death mediated by the gasdermin family of pore-forming proteins. Studies indicated that combining radiotherapy with pyroptosis greatly enhance the body's anti-tumor immunity and radiotherapy efficacy. In order to precisely control the location and intensity of cell scorch, an accurate and efficient cancer immunotherapy system was constructed by organically combining radiotherapy and pyrolysis with nanomaterials with infrared light and pH responsive regulatory protein expression. MATERIALS/METHODS An upconverting nanoparticles with integrated azobenzene-modified mesoporous silica was constructed to realize the controlled release of the drug (decitabine (DAC)) under the control of infrared light. Firstly, synthesis of UCNPS@mSiO2-azo. NaYF4: Tm, Yb@NaYF4 nanocrystals (UCNPS) was prepared by solvothermal method, and then UCNPS@mSiO2 was prepared by using cetyl trimethyl ammonium bromide (CTAB) as template and tetraethyl orthosilicate (TEOS) as silicon source. Finally, mesopores were formed by ion exchange method. UCNPS@mSiO2-azo is prepared by mixing UCNP@mSiO2 and N-(3-triethoxysilyl) propyl-4-phenylazobenzamide in ethanol at 80°C for 1 hour. Secondly, Synthesis of UCNPS@mSiO2-azo@DAC@HSA, (human serum albumin (HSA)). Disperse UCNPS@mSiO2-azo in PBS, add a certain amount of DAC and stir for 24h, add the polymerized HSA and react at 37°C for 3h to obtain UCNPS@mSiO2-azo@DAC@HSA. RESULTS The prepared UCNPS@mSiO2 with good up-conversion efficiency, which can convert infrared light into visible light and ultraviolet light (fig 1.a,c,d). At the same time, it was found that UCNPS@mSiO2-azo can effectively load the DAC, and at the same time it has good stability, and can controllably release the DAC under the control of infrared light (fig 1.b). More importantly, it was found through cell experiments that the cells would not die after adding materials and performing infrared light. However, once further low-dose radiotherapy treatment, the cells would experience obvious pyrosis. CONCLUSION A specific and highly sensitive radiotherapy immunosensitization system that can effectively enhance the therapeutic effect of tumors was constructed. It can regulate the specific protein content of tumor location in vivo by means of both internal and external sources of pH and infrared light with the combination of radiotherapy. This work provides a new treatment strategy for radiotherapy by changing the way of cell death to enhance the body's anti-tumor immunity after local treatment to effectively reduce the damage of normal cells and to effectively change the tumor suppression microenvironment and enhance its own anti-tumor immunity to completely eliminate tumors.