Dye/Peroxalate Aggregated Nanoparticles with Enhanced and Tunable Chemiluminescence for Biomedical Imaging of Hydrogen Peroxide

Hydrogen peroxide (H2O2) is an endogenous molecule that plays diverse physiological and pathological roles in living systems. Here we report multimolecule integrated nanoprobes with the enhanced chemiluminescence (Cl.) response to H2O2 that is produced in cells and in vivo. This approach is based on the nanoscopic coaggregation of a dye exhibiting aggregation-enhanced fluorescence (AEF) with a H2O2-responsive peroxalate that can convert chemical reaction energy into electronic excitation. The coaggregated CL nanoparticles (FPOA NPs) with an average size of similar to 20 nm were formulated by aqueous self-assembly of a ternary mixture of a surfactant (Pluronic F-127) and concentrated hydrophobic dye/peroxalte payloads. Spectroscopic studies manifest that FPOA NPs as a reagent-concentrated nanoreactor possess the signal enhancement effect by AEF, as well as the optimized efficiencies for H2O2 peroxalate reaction and subsequent intraparticle energy transfer to the dye aggregates, to yield greatly enhanced CL generation with a prolonged lifetime. It is shown that the enhanced CL signal thereby is capable of detecting intracellular H2O2 overproduced during immune response. We also demonstrate that the densely integrated nature of FPOA NPs facilitates further intraparticle Cl. energy transfer to a low-energy dopant to red shift the spectrum toward the biologically more transparent optical window, which enables the high-sensitivity in vivo visualization of H2O2 associated with early stage inflammation.