Biochemical Immune Modulation via Electron Relaxation for Enhanced Immunotherapy in Pancreatic Cancer

Regulating the function or expression of immune checkpoints is crucial for achieving effective immunotherapy. Previous studies have focused on the blocking effects of immune checkpoints and degradation strategies targeting mature immune checkpoint proteins. However, these approaches have shown limited success due to clinical efficacy constraints and technical challenges. Post-translational modifications of membrane proteins, particularly the proper formation of disulfide bonds, play a critical role in determining whether these proteins are expressed normally or degraded. In this study, we introduce a biochemical immune modulation strategy by using a polarization relaxation strategy, we first construct 131I encapsulated microporous barium titanate nanoparticles (I-mBTO) to induce sustained disulfide bond reduction in the endoplasmic reticulum (ER). This process disrupts the folding of CD47, leading to its degradation through the ubiquitin-proteasome system (UPS) and reduces CD47 expression on the cell membrane by 93.6%. Furthermore, the induced ER stress promotes the exposure of calreticulin (CRT) on the cell surface, increasing CRT levels by 2.8-fold. Our I-mBTOK nano-modulator efficiently enhances immune activity.