Potassium iodide enhances the anti-hepatocellular carcinoma effect of copper-cysteamine nanoparticle mediated photodynamic therapy on cancer treatment

As a novel photosensitizer, copper-cysteamine (Cu-Cy) nanoparticles (NPs) can enable photodynamic therapy (PDT) for cancer treatment with improved efficiency. Previous studies have demonstrated that potassium iodide (KI) can enhance anti-infection ability by increasing the release of reactive oxygen species (ROS). Herein, for the first time, we investigate whether KI can enhance the anti-hepatocellular carcinoma effect by Cu-Cy NPs based PDT. The results show that Cu-Cy NPs based PDT inhibited the growth, migration, and clone formation ability of HepG2, Hep3B, and Huh7 cells, and the inhibitory effect is enhanced largely after adding KI. The observations from calcein-AM and EthD-1 double fluorescence staining method, DAPI staining, and Annexin V-FITC/PI technology show that KI enhances the mortality rate of HepG2 cells through Cu-Cy NPs-mediated PDT and confirm the cell apoptosis with a significant rate. Further studies through flow cytometry have been found that KI can affect mitochondrial function by leading the mitochondrial membrane potential (MMP) decrease and enhance the intracellular ROS release through Cu-Cy NPs-mediated PDT. It also up-regulated p53 gene and protein expression, down-regulated surviving, decreased Bcl-2/Bax ratio, and activated caspase-3 and caspase-9 through PCR, and WB technology in cells and tissues. We theorize that the apoptosis mechanism may be caused by the up-regulation of p53 to activate the mitochondrial endogenous apoptosis pathway. Finally, using HepG2 bearing tumor model, we further confirmed that the combination of KI with Cu-Cy NPs-mediated PDT can inhibit tumor cell growth, which is a safe and effective modality without damaging healthy tissues. This study proposes Cu-Cy NPs combined with KI can enhance the efficacy of PDT anti-tumor therapy. The most likely products of the combination of Cu-Cy NPs and KI that are responsible for the enhanced PDT effects are singlet oxygen (¹O₂), biocidal triiodide (I₃⁻), and H₂O₂. Our research offers a new strategy for combined applications to improve the anti-tumor effect.