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.

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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.

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

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We utilized albumin as reducing agent to establish a novel pH-sensitive nanocarrier with abundant Cu⁺, which can encapsulate HDAC inhibitor vorinostat to form uniform V-CuNPs for synergistic chromatin remodelling and chemodynamic therapy.

The present study aimed to identify specific microRNAs (miRs) and their predicted target genes to clarify the molecular mechanisms of colorectal cancer (CRC). An miR expression profile (array ID, GSE39833), which consisted of 88 CRC samples with various tumor-necrosis-metastasis stages and 11 healthy controls, was downloaded from the Gene Expression Omnibus database. Subsequently, the differentially expressed miRs and their target genes were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways of target genes were analyzed using the Database for Annotation Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the target genes was constructed using the Search Tool for the Retrieval of Interacting Genes database. The present study identified a total of 18 differentially expressed miRs (upregulated, 8; downregulated, 10) in the sera of the CRC patients compared with the healthy controls. Of these, 3 upregulated (let-7b, miR-1290 and miR-126) and 2 downregulated (miR-16 and miR-760) differentially expressed miRs and their target genes, including cyclin D1 (CCND1), v-myc avian myelocytomatosis viral oncogene homolog (MYC), phosphoinositide-3-kinase, regulatory subunit 2 (beta) (PIK3R2) and SMAD family member 3 (SMAD3), were significantly enriched in the CRC developmental pathway. All these target genes had higher node degrees in the PPI network. In conclusion, let-7b, miR-1290, miR-126, miR-16 and miR-760 and their target genes, CCND1, MYC, PIK3R2 and SMAD3, may be important in the molecular mechanisms for the progression of CRC.