Xinze Li,Fan Wu,Dedong Yu,Xiayi Su,Kaikai Wang,Zhiwei Huang,Zhongqiu Lu
Neutrophil extracellular traps (NETs) and circulating cell-free DNA (cfDNA) are pivotal in driving excessive inflammation and organ damage during sepsis, with their levels correlating positively with sepsis severity in both patients and murine models. Despite the ability of deoxyribonuclease I (DNase I) to degrade NETs and cfDNA, its short half-life and rapid degradation limit its therapeutic effectiveness. To address this challenge, we developed a methyl-branched liposome fused with a red blood cell membrane for the systemic delivery of DNase I (DNase I/Rm-Lipo). The efficacy of DNase I/Rm-Lipo was evaluated in the stimulated immune cells and septic model. The data confirmed that DNase I/Rm-Lipo efficiently removed excess NETs and cfDNA in activated neutrophils. Following injection, DNase I/Rm-Lipo exhibited an extended circulation time, effectively suppressing neutrophil activation and regulating macrophage polarization to mitigate inflammation and prevent organ dysfunction in septic mice. These findings highlight the therapeutic potential of DNase I/Rm-Lipo as a promising candidate for sepsis management by targeting the degradation of NETs and cfDNA.
In this work, a potentiometric polyion sensing strategy based on the surface layer-enhanced transmembrane ion transfer is demonstrated. A polydopamine (PDA) nanolayer with negative charges is modified onto the surface of the polycation-sensitive electrode membrane and used to increase the ion fluxes from the sample phase to the membrane phase. Such modification can significantly improve the detection sensitivity of potentiometric polyion sensors through electrostatic interactions between cationic targets and anionic PDA groups, which can effectively promote the accumulation of the targets in the boundary layer of the organic membrane phase. By using a thin membrane protamine-sensitive electrode as a model, the detection sensitivity of the PDA-coated electrode (55 mV/μg·mL -1 ) is nearly five times higher than that of the unmodified electrode (12 mV/μg·mL -1 ). Moreover, the proposed surface PDA-modified polyion sensor can also be utilized as a general tool for sensitive detection of other polycationic targets and polyanionic species (e.g., the new cancer biomarker cell-free DNA). The proposed potentiometric sensing platform based on surface enhancement of ion transfer offers great potential for sensitive detection of various polyionic targets.
Chang Peng,Ting Fang,Hanjie Sun,Dongkai Wang,Ji Li
The clearance of cell-free DNA (cfDNA) in rheumatoid arthritis (RA) represents a promising therapeutic approach for inflammation. While cationic materials are widely utilized for cfDNA capture, their safety during in vivo delivery remains a critical concern. Additionally, macrophage-mediated inflammatory responses exacerbate disease progression. Here, we propose a charge-reversal and enhanced nanoassembly responsive to the inflammatory microenvironment, composed of a block polymer termed polycaprolactone-poly (N, N-dimethylacrylamide)-thioketal-polyethylene glycol (PCL-PDMA-TK-PEG, PPTP), a copolymer methoxy poly (ethylene glycol)-poly-l-lysine-2,3-dimethylmaleic anhydride (mPEG-PLL-DMA, PLM), and 4-octyl itaconate (4-OI). Charge reversal in acidic inflammatory microenvironments and ROS-responsive enhancement of positive surface charge, significantly improving cfDNA capture efficiency within inflammatory sites. Mitochondrial targeting through electrostatic interactions, promoting 4-OI release to inhibit macrophage-driven inflammation. Reduced protein shielding during systemic circulation, enabling precise accumulation in inflamed joints. The 4-OI@PPTP/PLM nanoassembly effectively suppresses inflammatory cytokine production, mitigates synovial hyperplasia, and attenuates bone erosion in collagen-induced arthritis models. This strategy integrates cfDNA scavenging with microenvironment reprogramming, offering a dual-action therapeutic platform for RA management.
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