Conjugated polymer nanoparticles, produced by in situ colloidal Knoevenagel polymerization, show advantageous properties (bright emission, colloidal/chemical stability and mesoscopic size range) that allow the successful in vivo application to real-time sentinel lymph node mapping in a mouse model.

Hydrogen peroxide (H(2)O(2)) 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 H(2)O(2) 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 H(2)O(2)-responsive peroxalate that can convert chemical reaction energy into electronic excitation. The coaggregated CL nanoparticles (FPOA NPs) with an average size of ~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 H(2)O(2) 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 H(2)O(2) 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 H(2)O(2) associated with early stage inflammation.

Water‐dispersed all‐in‐one nanoprobes composed of densely integrated peroxyoxalate fuel and a cyanine dye are formulated to optimize the nanoscopic chemiluminescence reaction. It is demonstrated that the chemiluminescent nanoformulation can generate bright near‐infrared signal in response to external hydrogen peroxide that is biologically implicated with cell signaling and diseases. Successful imaging of endogenously overproduces hydrogen peroxide and indirect determination of glucose level in vivo with the chemiluminescent nanoprobes offers an opportunity for early diagnosis of diseases.

Phthalocyanine-aggregated Pluronic nanoparticles were constructed as a novel type of near-infrared (NIR) absorber for photothermal therapy. Tiny nanoparticles (~ 60 nm, FPc NPs) were prepared by aqueous dispersion of phthalocyanine-aggregated self-assembled nanodomains that were phase-separated from the melt mixture with Pluronic. Under NIR laser irradiation, FPc NPs manifested robust heat generation capability, superior to an individual cyanine dye and cyanine-aggregated nanoparticles. Micro- and macroscopic imaging experiments showed that FPc NPs are capable of internalization into live cancer cells as well as tumor accumulation when intravenously administered into living mice. It is shown here that continuous NIR irradiation of the tumor-targeted FPc NPs can cause phototherapeutic effects in vitro and in vivo through excessive local heating, demonstrating potential of phthalocyanine-aggregated nanoparticles as an all-organic NIR nanoabsorber for hyperthermia.

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Nanoscopic dense integration between solid-state emission and photochromism provides nanoprobes capable of photoswitching of bright NIR fluorescence with high on/off contrast, bistability and improved signal identification, being suitable for imaging applications in autofluorescence-rich in vivo environments.

Dyes showing solid-state fluorescence (SSF) are intriguing molecules that can emit bright fluorescence in the condensed phase. Because they do not suffer from self-quenching of fluorescence, nanoscopic dense integration of those molecules produces particulate nanoprobes whose emission intensity can be boosted by raising the intraparticle dye density. In spite of the potential promise for imaging applications demanding intense emission signals, their excitation and emission spectra are generally limited to the visible region where biological tissues have less transparency. Therefore, the SSF-based nanoprobes have rarely been applied to noninvasive in vivo imaging. Here we report a combinatorial chemistry approach to attain a high level of tissue transparency of SSF by tuning its excitation and emission wavelengths to the truly near-infrared (NIR) region. We built a dipolar arylvinyl (ArV) scaffold-based chemical library where the optical bandgap could be narrowed to the NIR above 700 nm by combinatorial modulation of the π-electron push-pull strengths. The ArV-aggregated nanoparticles (FArV NPs) with a colloidal size less than 20 nm were formulated using a polymeric surfactant (Pluronic F-127) and applied to bioimaging in cells and in vivo. We demonstrate that some of FArV NPs have truly NIR excitation and emission of SSF, capable of noninvasive in vivo imaging (efficient lymph node mapping and early diagnosis of tumor) in mouse models by virtue of bright solid-state NIR fluorescence and high signal-to-background contrast (S/B ≈ 8) as well as facile circulation in the living body.