A Sierpiński-fractal supermolecule constructed lipid chemiluminescent nanosensor for mapping inflammatory status in murine models

Herein, a novel Sierpiński fractal material-based chemiluminescent (CL) nanosensor (CL-ST) capable of real-time mapping of singlet oxygen ( 1 O 2 ) dynamics and quantitative monitoring of inflammatory progression in murine models is presented. The CL-ST nanosensor is engineered through supramolecular self-assembly of Zn 2+ -coordinated terpyridine ligands (L1 and L2), followed by encapsulation within polyethylene glycol (PEG)-functionalized liposome to enhance biocompatibility. The formation of the supramolecular structure restricts the rotation of the terpyridine moieties in L1 and L2, resulting in the restriction of nonradiative exciton relaxation, which in turn enhances the fluorescence efficiency. As a result, the CL intensity of the supramolecular structure is 8–70 times higher than that of L1 and L2 nanoparticles, respectively. In vitro characterization reveals the lysosome-targeting capability and negligible cytotoxicity of CL-ST. Systemic toxicity assessments further confirm the nanosensor's biosafety profile, enabling efficient systemic delivery via peripheral circulation without eliciting significant biological perturbations. Capitalizing on the CL-ST nanosensor's exceptional selectivity and sensitivity towards 1 O 2 , this study pioneers the application of fractal materials in developing optical biosensors for in vivo biomarker monitoring. Through successful visualization of 1 O 2 generation in acute peritonitis and auricular edema models, the CL-ST platform achieves precise inflammatory site localization and quantitative inflammation status assessment through target/non-target (T/NT) photon ratio analysis. This research establishes a non-invasive methodology for dynamic inflammation tracking. The potential of fractal nanomaterials to construct innovative chemical and biochemical sensors for multidimensional disease diagnostics is anticipated.