Ultrabright Fluorescent Polymeric Nanoparticles Made from a New Family of BODIPY Monomers

Four novel BODIPY derivatives (π-) functionalized by different polymerizable groups, styrene (S), phenyl acrylate (PhA), ethyl methacrylate (EtMA) and ethyl acrylate (EtA) have been synthesized. Following a formerly established one-pot RAFT miniemulsion polymerization process (Grazon Macromol. Rapid Commun. 2011, 32, 699−705), the fluorophores were copolymerized in a controlled way at 2.6 mol % with styrene in water. On the basis of the polymerization-induced self-assembly (PISA) principle, the copolymers assembled during their formation into fluorescent nanoparticles. The distribution of the fluorescent monomers along the polymer backbone was monitored by kinetic studies of the copolymerization reaction. Fluorescent stationary and time-resolved spectroscopy was then performed on both the monomers and the nanoparticles (NPs) and the observed differences are discussed in view of the distribution of the fluorescent monomers in the polymer chain. With two of the novel fluorescent monomers (πS and πPhA), the brightness of the NPs could be significantly improved (by a factor 2) compared to particles comprising the other BODIPY monomers. The obtained particles were 200 to 2000 times brighter than usual quantum dots and 40 to 300 times brighter than most of the fluorescent polymeric nanoparticles reported in the literature

Ultrabright BODIPY-Tagged Polystyrene Nanoparticles: Study of Concentration Effect on Photophysical Properties

Fluorescent nanomaterials are invaluable tools for bioimaging. Polymeric nanoparticles labeled with organic dyes are very promising for this purpose. It is thus very important to fully understand their photophysical properties. New fluorescent core–shell nanoparticles have been prepared. The outer part is a poly­(ethylene glycol)-<i>block</i>-poly­(acrylic acid) copolymer, and the core is a copolymer of styrene and methacrylic BODIPY fluorophore. The hydrophilic and hydrophobic parts are covalently linked, ensuring both stability and biocompatibility. We prepared nanoparticles with increasing amounts of BODIPY, from 500 to 5000 fluorophores per particles. Increasing the concentration of BODIPY lowers both the fluorescence quantum yield and the lifetime. However, the brightness of the individual particles increases up to 8 × 10⁷. To understand the loss of fluorescence efficiency, fluorescence decays have been recorded and fitted with a mathematical model using a stretched exponential function. This result gives an insight into the fluorophore arrangement within the hydrophobic core

Fluorescent Labeling of a Bisurea-Based Supramolecular Polymer

Bisurea-based supramolecular polymer 2-ethylhexyl-3-[3-(3-(2-ethylhexyl)­ureido)-4-methyl-phenyl]­urea (EHUT) has been shown previously to self-assemble through hydrogen bonding into high-molecular-weight structures. The present publication reports the study of the thermodynamics of these tubular structures by time-resolved fluorescence spectroscopy, with the help of a tetrazine labeled monomer. Results of calorimetry and time-resolved fluorescence spectroscopy show that the as-modified monomer EHUTz does not interfere with the formation of the supramolecular assembly. When incorporated, these labeled monomers exhibit a longer fluorescence lifetime due to the electron-rich tolyl group buried in the structure. Dilution experiments allowed us to measure their partition coefficient, and to compare it with the critical aggregation concentration of EHUT. Measurements at higher dye loads, where interactions between neighboring tetrazines occur, show that EHUTz is uniformly dissolved in the supramolecular polymer. Tetrazine dye is a good reporter of events occurring in solution, such as disruption of the assembly upon heating. Our results confirm the pseudophase diagram for EHUT solution in toluene obtained previously with other techniques such as infrared spectroscopy and calorimetry

Understanding the Spectroscopic Properties and Aggregation Process of a New Emitting Boron Dipyrromethene (BODIPY)

Aggregation of organic dyes often has consequences on their spectroscopic properties in materials. Here, we study a new sterically hindered boron-dipyrromethene (BODIPY), with adamantyl moieties grafted for the first time on the BODIPY core. Its aggregation behavior was investigated in poly­(methyl methacrylate) (PMMA) and on drop-casted films by monitoring absorption, fluorescence emission, relative quantum yield (Φ_Fluo,Rel), lifetime and time-resolved anisotropy. Aggregates only appear from 0.067 mol·L^–1. A multicomponent analysis demonstrated that the aggregation process can be described by three distinguishable components which correspond to a monomer species (M) and J and H aggregates. The results also indicated a concentration frontier: when the dye concentration increased up to 0.29 mol·L^–1, the concentration of M decreased in favor of the aggregates. Φ_Fluo,Rel is yet only divided by 5 compared to the dye in solution. Above 0.29 mol·L^–1, an equilibrium between M and the J aggregates is established, showing meanwhile a steady Φ_Fluo,Rel. The J aggregates are found to be dimers, whereas the aggregation number is varying for the H aggregates. Analysis of fluorescence and anisotropy decays showed that the excitation energy was transferred from M to the J dimers, and very probably trapped by H aggregates

Understanding the Spectroscopic Properties and Aggregation Process of a New Emitting Boron Dipyrromethene (BODIPY)

Aggregation of organic dyes often has consequences on their spectroscopic properties in materials. Here, we study a new sterically hindered boron-dipyrromethene (BODIPY), with adamantyl moieties grafted for the first time on the BODIPY core. Its aggregation behavior was investigated in poly­(methyl methacrylate) (PMMA) and on drop-casted films by monitoring absorption, fluorescence emission, relative quantum yield (Φ_Fluo,Rel), lifetime and time-resolved anisotropy. Aggregates only appear from 0.067 mol·L^–1. A multicomponent analysis demonstrated that the aggregation process can be described by three distinguishable components which correspond to a monomer species (M) and J and H aggregates. The results also indicated a concentration frontier: when the dye concentration increased up to 0.29 mol·L^–1, the concentration of M decreased in favor of the aggregates. Φ_Fluo,Rel is yet only divided by 5 compared to the dye in solution. Above 0.29 mol·L^–1, an equilibrium between M and the J aggregates is established, showing meanwhile a steady Φ_Fluo,Rel. The J aggregates are found to be dimers, whereas the aggregation number is varying for the H aggregates. Analysis of fluorescence and anisotropy decays showed that the excitation energy was transferred from M to the J dimers, and very probably trapped by H aggregates

Sequential Copper-Catalyzed Alkyne–Azide Cycloaddition and Thiol-Maleimide Addition for the Synthesis of Photo- and/or Electroactive Fullerodendrimers and Cysteine-Functionalized Fullerene Derivatives

In this study, the functionalization of a fullerene building block in a stepwise process by means of the copper-catalyzed alkyne–azide cycloaddition (CuAAC) and thiol-maleimide reactions is reported. Grafting of the fullerene platform with a variety of azido derivatives, including Bodipy, pyrene and ferrocene, was carried out first. These fullerene compounds were then reacted with thiol derivatives to yield sophisticated structures comprising photo- and/or electroactive fullerodendrimers and cysteine-functionalized fullerene assemblies. This strategy, which combines the CuAAC and thiol-maleimide processes, could become more widely adopted in the field of fullerene chemistry

Biocompatible and Photostable Photoacoustic Contrast Agents as Nanoparticles Based on Bodipy Scaffold and Polylactide Polymers: Synthesis, Formulation, and <i>In Vivo</i> Evaluation

We have designed a new Bodipy scaffold for efficient in vivo photoacoustic (PA) imaging of nanoparticles commonly used as drug nanovectors. The new dye has an optimized absorption band in the near-infrared window in biological tissue and a low fluorescence quantum yield that leads to a good photoacoustic generation efficiency. After Bodipy-initiated ring-opening polymerization of lactide, the polylactide–Bodipy was formulated into PEGylated nanoparticles (NPs) by mixing with PLA–PEG at different concentrations. Formulated NPs around 100 nm exhibit excellent PA properties: an absorption band at 760 nm and a molar absorption coefficient in between that of molecular PA absorbers and gold NPs. Highly improved photostability compared to cyanine-labeled PLA NPs as well as innocuity in cultured macrophages were demonstrated. After intravenous injection in healthy animals, NPs were easily detected using a commercial PA imaging system and spectral unmixing, opening the way to their use as theranostic agents