Macrophage-Mimic Hollow Mesoporous Fe-Based Nanocatalysts for Self-Amplified Chemodynamic Therapy and Metastasis Inhibition via Tumor Microenvironment Remodeling.

Fe-based nanomaterials with Fenton reaction activity are promising for tumor-specific chemodynamic therapy (CDT). However, most of the nanomaterials suffer from low catalytic efficiency due to its insufficient active site exposure and the relatively high tumor intracellular pH, which greatly impede its clinical application. Herein, macrophage membrane-camouflaged carbonic anhydrase IX inhibitor (CAI)-loaded hollow mesoporous ferric oxide (HMFe) nanocatalysts are designed to remodel the tumor microenvironment with decreased intracellular pH for self-amplified CDT. The HMFe not only serves as a Fenton agent with high active-atom exposure to enhance CDT but also provides hollow cavity for CAI loading. Meanwhile, the macrophage membrane-camouflaging endows the nanocatalysts with immune evading capability and improves tumoritropic accumulation by recognizing tumor endothelium and cancer cells through α4/VCAM-1 interaction. Once internalized by tumor cells, the CAI could be specifically released, which can not only inhibit CA IX to induce intracellular H+ accumulation for accelerating the Fenton reaction but also could prevent tumor metastasis because of the insufficient H+ formation outside cells for tumor extracellular matrix degradation. In addition, the HMFe can be employed to highly efficient magnetic resonance imaging to real-time monitor the agents' bio-distribution and treatment progress. Both in vitro and in vivo results well demonstrated that the nanocatalysts could realize self-amplified CDT and breast cancer metastasis inhibition via tumor microenvironment remodeling, which also provides a promising paradigm for improving CDT and antimetastatic treatment.

Association Between miR-149 Gene rs2292832 Polymorphism and Risk of Gastric Cancer.

BACKGROUND AND AIMS: Accumulating evidence suggested that microRNA (miRNA) genes take part in different processes associated with gastric cancer (GC). The single nucleotide polymorphisms (SNPs) located on miRNA sequences may affect the interaction with their target mRNAs and consequently the genetic susceptibility to GC. MATERIALS/METHODS: A hospital-based case-control study with 320 cases and 354 controls was conducted to investigate the association between miR-149 gene rs2292832 polymorphism and GC susceptibility in a Chinese Han population. RESULTS: TT genotype or T allele carriers of miR-149 gene rs2292832 polymorphism increased the risk of GC. Furthermore, a meta-analysis together with this study between this SNP and GC risk was performed. In the allele association study, meta-analysis between this polymorphism and GC risk showed that T or C allele was not associated with the risk of GC, but TC genotype carriers of miR-149 gene rs2292832 polymorphism were associated with decreased risk of GC (TC vs. CC, heterozygote model: OR and 95% CI, 0.80 [0.67,0.96]). Stratification analysis of ethnicity in this meta-analysis indicated that rs2292832 polymorphism decreased the risk of GC among Caucasians (TT  + TC vs. CC, dominant model: OR and 95% CI, 0.69 (0.50,0.97); TC vs. CC, heterozygote model: OR and 95% CI, 0.68 [0.47,0.97]), while this SNP increased the risk of GC among Asians (TT vs. TC  + CC, recessive model: OR and 95% CI, 1.24 [1.04,1.48]; T vs. C, allele model: OR and 95% CI, 1.13 [1.00,1.28]). CONCLUSION: This case-control study and meta-analysis confirm that miR-149 gene rs2292832 polymorphism is associated with increased risk of GC among Asians.