Zhuoqun Su,Wanxiao Wang,Liuxin Jiao,Jingxian Hou,Jianing Chen,Ying Wang,Di Wu,Yongning Wu,Guoliang Li
DNA repair intermediates such as abasic (AP) sites are among the most abundant and reactive DNA lesions. Despite their central roles in repair fidelity and as therapeutic targets, their transient dynamics and covalent reactivity remain difficult to probe with existing methods. Here, we introduce a molecular anchor-assisted strategy that immobilizes AP-containing ssDNA within the α-hemolysin (α-HL) nanopore, enabling real-time monitoring of its reactivity dynamics. Vitamin B12 is covalently attached to thiol-modified ssDNA through a cobalt–sulfur bond, serving as a molecular anchor to tether ssDNA inside the α-HL nanopore. The resulting B12-anchored ssDNA produces uniform current blockages of defined amplitude. This approach allows high-resolution discrimination of the four canonical nucleobases and dynamic tracking of AP site formation. By recording the reactions of hydroxylamine compounds with AP sites, we discovered that different substituent groups on hydroxylamines modulate their reactivity toward AP sites. Furthermore, this B12-anchored ssDNA strategy functions as a single-molecule reactor, enabling the capture of transient chemical structural changes at AP sites and direct observation of their reaction processes with nucleophilic agents at the single-molecule level. The results demonstrate that nanopore-based single-molecule profiling enables detailed kinetic and mechanistic studies of reactive DNA intermediates, which are otherwise difficult to monitor, thereby highlighting its potential for molecular diagnostics and targeted therapeutic development.
Metformin is currently the most commonly used oral drug for the treatment of diabetes. However, excessive use can up-regulate hydrogen sulfide (H 2 S) levels in the liver, which subsequently leads to severe liver injury and hepatotoxicity. Therefore, using endogenous H 2 S as a target molecule of an intelligent triggering sensor, a nano-probe that can recognize H 2 S with high specificity, and achieve non-invasive and highly specific in situ second near-infrared (NIR-II) photoacoustic (PA) imaging of hepatotoxicity induced by metformin would be welcomed in the field. In this work, we designed and synthesized a smart-responsive PA sensor based on metal-organic framework as bioreactor to dynamically monitor the changes in H 2 S levels induced by metformin. Molecular sieve imidazole framework-8 (ZIF-8) was selected as the coating layer, and the unique pore size of ZIF-8 was used to improve the selectivity of the sensor to H 2 S. The designed CuO x NPs@MOFs sensor turned on the PA signal of the sensor in NIR-II by in situ sulfation with overexpressed endogenous H 2 S in injured liver tissues. More importantly, the changes in the PA signal could non-invasively monitor liver injury in real time and with high sensitivity. Utilizing the unique structure in the MOFs sensor to selective recognize H 2 S molecules, ultra-sensitive monitoring and PA imaging of H 2 S in vitro and in vivo were achieved.
Wenhui Zhang,Min Zhao,Leqiang Wang,Jiaqi Wang,Xiaoguang Ge,Junzhi Liu,Bin Chen,Shi Gao,Jingbin Lu
Metal-organic frameworks (MOFs) based on nanomaterials have attracted attention for tumor microenvironment (TME)-responsive therapy. However, they lack intrinsic imaging capabilities to monitor drug release and predict therapeutic outcomes. Herein, metal-phenolic nanosheets (Cu/EA-MOF) with photoacoustic (PA) imaging property in the second near-infrared window were constructed to achieve diagnosis and treatment for H 2 S-enriched tumors. Endogenous H 2 S triggers the decomposition of Cu/EA-MOF into the ellagic acid (EA) and copper sulfide (Cu 2-x S), which can be used for chemotherapy and chemodynamic therapy, respectively. Moreover, EA can enhance the efficiency of chemodynamic therapy by boosting superoxide dismutase activity. Importantly, the degradation of Cu/EA-MOF can be indicated via the change of ratiometric PA signal intensity. Furthermore, the NIR-II fluorescent molecule benzobisthiadiazole (BBT) was further introduced into Cu/EA-MOF to investigate the degradation process and drug release. As a promising theranostic nanomaterial, Cu/EA/BBT-MOF is successfully used to achieve effective synergistic therapy and predict therapeutic outcomes.
危险品化学品经营许可证（带存储）