Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to radiation therapy. To overcome hypoxia-induced radiation resistance, recent studies have described nanosystems to improve tumor oxygenation for immobilizing DNA damage and simultaneously initiate oxygen-dependent HIF-1α degradation. However, HIF-1α degradation is incomplete during tumor oxygenation treatment alone. Therefore, tumor oxygenation combined with residual HIF-1 functional inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a reactive oxygen species (ROS) responsive nanoplatform is reported to successfully add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive nanoplatform, based on manganese dioxide (MnO) nanoparticles, delivers the HIF-1 inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues. After reacting with overexpressed hydrogen peroxide (HO) within tumor tissues, Mn and oxygen molecules are released for magnetic resonance imaging and tumor oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is obviously decreased to reduce the risk of metastasis. Furthermore, the nanoplatform could relieve T-cell exhaustion via downregulation of PD-L1, whose effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently activates tumor-specific immune responses against abscopal tumors. These therapeutic benefits including increased X-ray-induced damage, downregulated resistance, and T-cell exhaustion related proteins expression achieved synergistically the optimal inhibition of tumor growth. Overall, this designed ROS responsive nanoplatform is of great potential in the sensitization of radiation for combating primary and metastatic tumors.

No abstract

Insufficient T‐cell infiltration seriously hinders the efficacy of tumor immunotherapy. Induction of immunogenic cell death (ICD) is a potentially feasible approach to increase T‐cell infiltration. Since ionizing radiation can only induce low‐level ICD, this study constructs Cu‐based nanoscale coordination polymers (Cu‐NCPs) with mixed‐valence (Cu+/Cu2+), which can simultaneously and independently induce the generation of Cu+‐triggered hydroxyl radicals and Cu2+‐triggered GSH elimination, to synergize with radiation therapy for potent ICD induction. Markedly, this synergetic therapy remarkably enhances dendritic cell maturation and promotes antitumor CD8+ T‐cell infiltration, thereby potentiating the development of checkpoint blockade immunotherapies against primary and metastatic tumors.

No abstract

A biofunctional liposome containing acriflavine (ACF) and doxorubicin (DOX) for reducing the chemotherapy resistance of DOX induced by reactive oxygen species.