RESUMEN
The combined treatment with nanoparticles and autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine (HCQ), is extensively explored for cancer therapy. However, the toxicity of autophagy inhibitors and their unselective for tumoricidal autophagy have seriously hindered the application of the combined treatment. In this study, a carboxy-functional iron oxide nanoparticle (Fe2O3@DMSA) is designed and identified to significantly exert an antitumor effect without adding CQ or HCQ. Further investigation indicates that the effective inhibition effect of Fe2O3@DMSA alone on hepatoma growth is triggered by inhibiting the fusion of autophagosomes and lysosomes to enhance tumoricidal autophagy, which is induced by intracellular iron-retention-induced sustained reactive oxygen species (ROS) production. Furthermore, in two hepatoma-bearing mouse models, Fe2O3@DMSA alone effectively suppresses the growth of tumors without obvious toxic side effects. These studies offer a promising strategy for cancer therapy.
RESUMEN
Unmethylated CpG oligodeoxynucleotides are potent immunostimulatory motifs in activating both innate and acquired immune system by inducing Th1 type antigen-specific T cell responses, but their instability in serum greatly influences their immunostimulant efficiency. Here, we constructed a novel immuno-DNA nanohydrogels consisting of tandem repeat sequences of CpG units named CpG-MCA nanohydrogels through multi-primed chain amplification. CpG-MCA nanohydrogels were proved to resist degradation and increase the proliferation and migration of murine macrophage-like RAW264.7 cells. Furthermore, CpG-MCA nanohydrogels effectively induced high expression of tumor necrosis factor-α and interleukin-6, and remarkably inhibited the proliferation of U251 cells, suggesting that CpG-MCA nanohydrogels are expected to be employed as the potent anti-cancer immunostimulant.