Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents.

Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives (1-3) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and 1 O2 emission were obtained only under acidic conditions inducing amine protonation. The pKa values and pH-dependent emissive properties of 1-3 being established, their cellular uptake and activation in the lysosomal vesicles (pH≈4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC50 between 0.16 and 0.06 µM) against HeLa cancer cells.

Synthesis and Optical Properties of Excited-State Intramolecular Proton Transfer (ESIPT) Emitters with Sulfobetaine Fragments.

This article describes the synthetic efforts towards the solubilization of organic fluorescent emitters based on a 2-(2'-hydroxybenzofuranyl)benzazole (HBBX) scaffold in aqueous media under physiological conditions (PBS, pH 7.4). These dyes are well-known to display the excited-state intramolecular proton transfer (ESIPT) process which leads to a Stokes-shifted fluorescence with enhanced photostability and strong environment dependent features. Organic dyes are hydrophobic by nature and their vectorization into aqueous media usually necessitates amphiphilic polymers. In this study, we show that the incorporation of one or two sulfobetaine fragments, a highly biocompatible zwitterionic unit leads to the vectorization in buffer solution at pH 7.4 while keeping a reasonable ESIPT fluorescence emission. The photophysical properties of all dyes were studied in multiple solvents and showed that, depending on structure and environment, different excited-state species are observed: normal or tautomeric species, as well as a competitive anionic fluorescent derivative. This study shows that it is not only possible to solubilize fluorescent ESIPT dyes in water using sulfobetaine(s) but also that the optical properties can be finely tuned depending on small structural inputs.

Ultra-Narrow-Band NIR Photomultiplication Organic Photodetectors Based on Charge Injection Narrowing.

Ultra-narrow-band NIR photomultiplication organic photodetectors (PM-OPDs) were realized in ITO/PEDOT:PSS/active layers/Al based on an interfacial-trap-induced charge injection narrowing (CIN) concept. The rather less Bod Ethex-Hex (BEH) is imbedded in a polymer donor matrix to form large amounts of isolated electron traps. Trapped electrons in BEH close to an Al electrode will enforce hole-tunneling injection induced by interfacial band bending, resulting in a photomultiplication phenomenon. PM-OPDs with P3HT:BEH as the active layer exhibit a narrow response peak at 850 nm with a full-width at half-maximum (fwhm) of 27 nm as well as a rather weak response from 650 to 800 nm. The EQE of 29 700% at 850 nm was achieved in PM-OPDs by incorporating 0.02 wt % of F6TCNNQ under -13 V of applied voltage. The rejection ratio (RR) of the optimized PM-OPDs with F6TCNNQ is 11 for EQE850 nm/EQE700 nm and 10 for EQE850 nm/EQE750 nm, respectively. An EQE of 15 300% at 850 nm was achieved in the ternary PM-OPDs under -13 V of applied voltage, with markedly enhanced RRs of 44 for EQE850 nm/EQE700 nm and 30 for EQE850 nm/EQE750 nm.

Fluorine-18-Labeled Fluorescent Dyes for Dual-Mode Molecular Imaging.

Recent progress realized in the development of optical imaging (OPI) probes and devices has made this technique more and more affordable for imaging studies and fluorescence-guided surgery procedures. However, this imaging modality still suffers from a low depth of penetration, thus limiting its use to shallow tissues or endoscopy-based procedures. In contrast, positron emission tomography (PET) presents a high depth of penetration and the resulting signal is less attenuated, allowing for imaging in-depth tissues. Thus, association of these imaging techniques has the potential to push back the limits of each single modality. Recently, several research groups have been involved in the development of radiolabeled fluorophores with the aim of affording dual-mode PET/OPI probes used in preclinical imaging studies of diverse pathological conditions such as cancer, Alzheimer's disease, or cardiovascular diseases. Among all the available PET-active radionuclides, 18F stands out as the most widely used for clinical imaging thanks to its advantageous characteristics (t1/2 = 109.77 min; 97% ß+ emitter). This review focuses on the recent efforts in the synthesis and radiofluorination of fluorescent scaffolds such as 4,4-difluoro-4-bora-diazaindacenes (BODIPYs), cyanines, and xanthene derivatives and their use in preclinical imaging studies using both PET and OPI technologies.

Water-soluble BODIPY derivatives.

New, water-soluble BODIPY dyes have been readily obtained from various BODIPY cores by reactions involving the introduction of novel sulfonated peptide chains by either coupling or substitution to give dimethylpropargylamine derivatives subsequently quaternized by reaction with propanesultone.

Solid-state gas sensors developed from functional difluoroboradiazaindacene dyes.

This article describes the synthesis and characterization of several new difluoroboradiazaindacene (BODIPY) dyes functionalized at the central 8-position by a phenyliodo, phenylheptynoate or phenylheptynoic fragment and at the 3- or 3/5-position(s) by 4-dimethylaminophenylstyryl residue(s). Single-crystal structural determinations confirm the planarity of the dyes, while the absorption and fluorescence spectroscopic properties are highly sensitive to the state of protonation (or alkylation) of the terminal anilino donor group(s). Reversible color tuning from green to blue for absorption and from colorless (i.e., near-IR region) to red for fluorescence is obtained on successive addition of acid and base. The difunctionalized derivative is especially interesting in this respect and shows two well-resolved pK(a) values of 5.10 and 3.04 in acetonitrile. Addition of the first proton causes only small spectral changes and deactivates the molecule towards addition of the second proton. It is this latter step that accommodates the large change in absorption and emission properties, due to the reversible extinction of the intramolecular charge-transfer character inherent to this type of dye. The main focus of the work is the covalent anchoring of the dyes to inert, porous polyacrylate beads so as to form a solid-state sensor suitable for analysis of gases or flowing liquids. The final material is highly stable--its performance is undiminished after more than one year--and fully reversible over many cycles. The sensitivity is such that reactions can be followed by the naked eye and the detection limit is about 600 ppb for HCl and about 80 ppb for ammonia. Trace amounts of diphosgene can be detected, as can alkylating agents. The sensing action is indiscriminate and also operates when the beads are dispersed in aqueous media.