Distyryl Boron Dipyrromethene Research Articles

Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light.

Boron-dipyrromethene (BODIPY) dyes are promising photosensitizers for cellular imaging and photodynamic therapy (PDT) owing to their excellent photophysical properties and the synthetically tunable core. Metalation provides a convenient way to overcome the drawbacks arising from their low aqueous solubility. New photo-/redox-responsive Co(III) prodrug chaperones are developed as anticancer PDT agents for efficient cellular delivery of red-light-active BODIPY dyes. The photobiological activity of heteroleptic Co(III) complexes derived from tris(2-pyridylmethyl)amine (TPA) and acetylacetone-conjugated PEGylated distyryl BODIPY (HL1) or its dibromo analogue (HL2), [CoIII(TPA)(L1/L2)](ClO4)2 (1 and 2), are investigated. The Co(III)/Co(II) redox potential is tuned using the Co(III)-TPA scaffold. Complex 1 displays the in vitro release of BODIPY on red light irradiation. Complex 2, having good singlet oxygen quantum yield (ΦΔ ∼ 0.28 in DMSO), demonstrates submicromolar photocytotoxicity to HeLa cancer cells (IC50 ≈ 0.23 μM) while being less toxic to HPL1D normal cells in red light. Cellular imaging using the emissive complex 1 shows mitochondrial localization and significant penetration into the HeLa tumor spheroids. Complex 2 shows supercoiled DNA photocleavage activity and apoptotic cell death through phototriggered generation of reactive oxygen species. The Co(III)-BODIPY prodrug conjugates exemplify new type of phototherapeutic agents with better efficacy than the organic dyes alone in the phototherapeutic window.

A near-infrared emitting “off-on” fluorescent probe for bioimaging of Pd(Ⅱ) ions in living cells and mice

BackgroundThe surging consumption of palladium in modern industry has given rise to its accumulation in the ecosystem, posing conspicuous toxicity to aquatic organisms and human health. The investigation of palladium in biological systems is highly demanded for the in-depth understanding of its dynamics and behaviors. Fluorescence imaging serves as a powerful approach to assess palladium species in biological systems, and currently most of the sensing probes are applicable to living cells. Effective tracking of palladium species in living organisms is challenging, which requires sufficient hydrophilicity and imaging depth of the probes. ResultsBased on an intramolecular charge transfer (ICT) mechanism, a distyryl boron dipyrromethene (BODIPY) derivative (DISBDP-Pd) has been prepared for the near-infrared (NIR) fluorescence imaging of Pd2+ ions. Two additional methoxy triethylene glycol (TEG) chains could serve as flexible and hydrophilic moieties to enhance the aqueous solubility and cell permeability of the extended conjugate. Solution studies revealed that DISBDP-Pd exhibited a NIR fluorescence enhancement signal exclusively to Pd2+ ions (detection limit as low as 0.85 ppb) with negligible interference from Pd0 species and other closely related metal ions. Computational calculations have been performed to rationalize the binding mode and the mechanism of action. Fluorescence imaging assays have been conducted on A549 human non-small cell lung carcinoma cells and mouse models. Exhibiting negligible cytotoxicity, DISBDP-Pd demonstrated concentration-related fluorescence enhancement signals in response to Pd2+ ions in living cells and mice. SignificanceDISBDP-Pd exhibits advantages over many small molecule palladium probes in terms of satisfactory aqueous solubility, high sensitivity and selectivity, and biocompatible NIR emission property, which are particularly favorable for the sensing application in biological environments. The design strategy of this probe can potentially be adopted for the functionalization of other BODIPY probes implemented for NIR fluorescence bioimaging.

Enzyme-Responsive Double-Locked Photodynamic Molecular Beacon for Targeted Photodynamic Anticancer Therapy

An advanced photodynamic molecular beacon (PMB) was designed and synthesized, in which a distyryl boron dipyrromethene (DSBDP)-based photosensitizer and a Black Hole Quencher 3 moiety were connected via two peptide segments containing the sequences PLGVR and GFLG, respectively, of a cyclic peptide. These two short peptide sequences are well-known substrates of matrix metalloproteinase-2 (MMP-2) and cathepsin B, respectively, both of which are overexpressed in a wide range of cancer cells either extracellularly (for MMP-2) or intracellularly (for cathepsin B). Owing to the efficient Förster resonance energy transfer between the two components, this PMB was fully quenched in the native form. Only upon interaction with both MMP-2 and cathepsin B, either in a buffer solution or in cancer cells, both of the segments were cleaved specifically, and the two components could be completely separated, thereby restoring the photodynamic activities of the DSBDP moiety. This PMB could also be activated in tumors, and it effectively suppressed the tumor growth in A549 tumor-bearing nude mice upon laser irradiation without causing notable side effects. In particular, it did not cause skin photosensitivity, which is a very common side effect of photodynamic therapy (PDT) using conventional "always-on" photosensitizers. The overall results showed that this "double-locked" PMB functioned as a biological AND logic gate that could only be unlocked by the coexistence of two tumor-associated enzymes, which could greatly enhance the tumor specificity in PDT.

Highly Efficient Far-Red/NIR-Absorbing Neutral Ir(III) Complex Micelles for Potent Photodynamic/Photothermal Therapy.

A critical issue in photodynamic therapy (PDT) is inadequate reactive oxygen species (ROS) generation in tumors, causing inevitable survival of tumor cells that usually results in tumor recurrence and metastasis. Existing photosensitizers frequently suffer from relatively low light-to-ROS conversion efficiency with far-red/near-infrared (NIR) light excitation due to low-lying excited states that lead to rapid non-radiative decays. Here, a neutral Ir(III) complex bearing distyryl boron dipyrromethene (BODIPY-Ir) is reported to efficiently produce both ROS and hyperthermia upon far-red light activation for potentiating in vivo tumor suppression through micellization of BODIPY-Ir to form "Micelle-Ir". BODIPY-Ir absorbs strongly at 550-750nm with a band maximum at 685nm, and possesses a long-lived triplet excited state with sufficient non-radiative decays. Upon micellization, BODIPY-Ir forms J-type aggregates within Micelle-Ir, which boosts both singlet oxygen generation and the photothermal effect through the high molar extinction coefficient and amplification of light-to-ROS/heat conversion, causing severe cell apoptosis. Bifunctional Micelle-Ir that accumulates in tumors completely destroys orthotopic 4T1 breast tumors via synergistic PDT/photothermal therapy (PTT) damage under light irradiation, and enables remarkable suppression of metastatic nodules in the lungs, together without significant dark cytotoxicity. The present study offers an emerging approach to develop far-red/NIR photosensitizers toward potent cancer therapy.

Immobilising hairpin DNA-conjugated distyryl boron dipyrromethene on gold@polydopamine core-shell nanorods for microRNA detection and microRNA-mediated photodynamic therapy.

A novel nanosystem of polydopamine-coated gold nanorods (AuNR@PDA) immobilised with molecules of hairpin DNA-conjugated distyryl boron dipyrromethene (DSBDP) was designed and fabricated for detection of microRNA-21 (miR-21). By using this oncogenic stimulus, the photodynamic effect of the DSBDP-based photosensitiser was also activated. In the presence of miR-21, the fluorescence intensity of the nanosystem was increased due to the dissociation of the conjugate from AuNR@PDA upon hybridisation. The intracellular fluorescence intensity triggered by intracellular miR-21 was in the order: MCF-7 > HeLa > HEK-293, which was in accordance with their miR-21 expression levels. The specificity was demonstrated by comparing the results with those of an analogue with a scrambled DNA sequence. The nanosystem could also result in miR-21-mediated photodynamic eradication of miR-21-overexpressed MCF-7 cells. After intravenous injection of the nanosystem into HeLa tumour-bearing nude mice, the fluorescence intensity of the tumour was increased over 24 h and was about 3-fold stronger than that of the scrambled analogue. Upon irradiation, the nanosystem could also greatly reduce the size of the tumour without causing significant tissue damage in the major organs. The overall results showed that this nanoplatform can serve as a specific and potent theranostic agent for simultaneous miR-21 detection and miR-21-mediated photodynamic therapy.

A novel distyryl boron dipyrromethene with two functional tags for site-specific bioorthogonal photosensitisation towards targeted photodynamic therapy.

A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice.

A H₂O₂-Responsive Boron Dipyrromethene-Based Photosensitizer for Imaging-Guided Photodynamic Therapy.

In this study, we demonstrate a novel H2O2 activatable photosensitizer (compound 7) which contains a diiodo distyryl boron dipyrromethene (BODIPY) core and an arylboronate group that quenches the excited state of the BODIPY dye by photoinduced electron transfer (PET). The BODIPY-based photosensitizer is highly soluble and remains nonaggregated in dimethyl sulfoxide (DMSO) as shown by the intense and sharp Q-band absorption (707 nm). As expected, compound 7 exhibits negligible fluorescence emission and singlet oxygen generation efficiency. However, upon interaction with H2O2, both the fluorescence emission and singlet oxygen production of the photosensitizer can be restored in phosphate buffered saline (PBS) solution and PBS buffer solution containing 20% DMSO as a result of the cleavage of the arylboronate group. Due to the higher concentration of H2O2 in cancer cells, compound 7 even with low concentration is particularly sensitive to human cervical carcinoma (HeLa) cells (IC50 = 0.95 μM) but hardly damage human embryonic lung fibroblast (HELF) cells. The results above suggest that this novel BODIPY derivative is a promising candidate for fluorescence imaging-guided photodynamic cancer therapy.

Synthesis of novel monostyryl and distyryl boron dipyrromethenes bearing 4-((2-hydroxyethyl)(methyl)amino group as cholinesterase and tyrosinase inhibitors

Abstract In this study, the synthesis of novel Monostyryl and Distyryl boron dipyrromethene dyes containing 4-((2-hydroxyethyl)(methyl)amino) group to determine neuroprotective potential has been reported for the first time. They were synthesized starting from BODIPY dye 1. Their inhibitory properties against Acetylcholinesterase/Butyrylcholinesterase (AChE/BuChE) and tyrosinase (Tyr) were evaluated according to Ingkaninan’s and Masuda’s methods and kinetic analysis of compounds was done using Lineweaver-Burk and Dixon plots.

Push–Pull Distyryl Boron Dipyrromethenes as Near‐Infrared Sensitizers for Dye‐Sensitized Solar Cells

AbstractA diiodo distyryl boron dipyrromethene (BODIPY) with an ethyl ester group at the meso position was prepared. This compound underwent palladium‐catalyzed Sonogashira cross‐coupling reactions with 4‐(diphenylamino)phenylethyne and 4‐(dimethylamino)phenylethyne to give the corresponding dialkynyl derivatives. After alkaline hydrolysis and acidic work‐up, all three compounds were converted to the carboxyl analogues, which could bind to the surface of TiO2 for application in dye‐sensitized solar cells (DSSCs). These compounds, in particular the dialkynyl analogues, possessed a push–pull structure and a highly conjugated π system, which shifted the Q band to the near‐infrared region. Electrochemical studies revealed that they had appropriate HOMO and LUMO levels for the construction of DSSCs comprising a TiO2 electrode and an electrolyte containing an I3−/I− redox couple. The optimized structures, frontier molecular orbitals, and absorption spectra of these sensitizers were calculated using density functional theory. The diiodo distyryl BODIPY‐based DSSC showed a photovoltaic conversion efficiency of 2.78 % under AM 1.5G standard sunlight and a maximum incident photon‐to‐current conversion efficiency (IPCE) of >45 % at 780 nm. The DSSCs fabricated with the dialkynyl distyryl BODIPYs could achieve an IPCE value of approximately 20 % at 840 nm and a broader photoresponse over the whole visible range extending up to approximately 950 nm in the near‐infrared region.

Light harvesting systems composed of carbazole based subphthalocyanine-BODIPY enhanced with intramolecular fluorescence resonance energy transfer (FRET)

A new series of subphthalocyanine-borondipyrromethene scaffolds containing N-ethylcarbazole moiety have been successfully designed and synthesized. The identities of synthesized compounds were confirmed by using 1H, 13C NMR, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The photophysical properties of the newly synthesized subphthalocyanine-borondipyrromethene conjugates were investigated via absorption and fluorescence spectroscopies in dichloromethane, tetrahydrofuran, benzene, and toluene solution (1 × 10−5 M). The targeted compounds exhibit a highly efficient energy transfer process, either from the excited borondipyrromethene to the subphthalocyanine core or from the excited subphthalocyanine to the mono or distyryl borondipyrromethene unit. The time resolved fluorescence studies of the subphthalocyanine- borondipyrromethene conjugates were also examined.

PH- and Thiol-Responsive BODIPY-Based Photosensitizers for Targeted Photodynamic Therapy.

A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid-labile ketal and/or thiol-cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron-transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively. The separation of the BODIPY core and the ferrocenyl moieties restored the photoactivities of the former in phosphate buffered saline and inside the MCF-7 breast cancer cells, rendering these compounds as potential activable photosensitizers for targeted photodynamic therapy. The dual activable analogue exhibited the greatest enhancement in intracellular fluorescence intensity in both an acidic environment (pH 5) and the presence of DTT (4 mm). Its photocytotoxicity against MCF-7 cells also increased by about twofold upon preincubation with 4 mm of DTT. The activation of this compound was also demonstrated in nude mice bearing a HT29 human colorectal carcinoma. A significant increase in fluorescence intensity in the tumor was observed over 9 h after intratumoral injection.

BODIPY‐Based Nanomicelles as Near‐Infrared Fluorescent “Turn‐On” Sensors for Biogenic Thiols

AbstractWe report novel, aqueous, soluble, distyryl boron dipyrromethene (BODIPY)‐containing nanomicelles as biogenic thiol sensors with near‐infrared (NIR) “turn‐on” properties. The average hydrodynamic diameter of these nanomicelles is 30 nm. They show good photostability, are selective towards biogenic thiols, and function within a broad pH window (pH 3–10). Near‐infrared‐emitting distyryl‐BODIPY was chemically linked to fluorescence quencher group of 2,4‐dinitrobenzenesulfonyl (DNBS) and was then water solubilized and formed into nanomicelles via polylactic acid‐polyethylene glycol (PLA‐PEG) encapsulation. When thiols react with the DNBS moiety, we observe subsequent recovery of distyryl‐BODIPY fluorescence both in vitro and in living cells. This work provides a simple and general method to construct intracellular nanoprobes for biogenic thiols and may pave the way to the development other fluorescence‐dye‐based sensors.

Preparation and in Vitro Photodynamic Activities of Folate-Conjugated Distyryl Boron Dipyrromethene Based Photosensitizers

Two folate-conjugated diiododistyryl boron dipyrromethenes have been prepared and characterized with various spectroscopic methods. These conjugates exhibit higher photocytotoxicity toward the KB human nasopharyngeal carcinoma cells, which have high expression of folate receptors when compared with the MCF-7 human breast adenocarcinoma cells, which have low expression of folate receptors. The difference in photocytotoxicity for these two cell lines is particularly large for the conjugate with a shorter oligoethylene glycol linker (compound 11a) as a result of its higher cellular uptake and slightly lower aggregation tendency. Its IC50 value toward KB cells (0.06 μM) is 43-fold lower than that for MCF-7 cells, while the difference is only 6-fold for the analogue with a longer linker (compound 11b). The length of the spacer also affects their subcellular localization. While compound 11a shows high affinity toward the endoplasmic reticulum of KB cells, conjugate 11b is mainly localized in the lysosomes.

A Highly Selective Colorimetric and Fluorescent Probe for Cu2+ and Hg2+ Ions Based on a Distyryl BODIPY with Two Bis(1,2,3‐triazole)amino Receptors

A new distyryl boron dipyrromethene (BODIPY) with two bis(1,2,3-triazole)amino substituents has been prepared by typical Knoevenagel condensation followed by click reaction. The compound selectively binds to Cu(2+) and Hg(2+) ions in CH(3)CN/H(2)O (1:1 v/v) to give remarkably blueshifted electronic absorption and fluorescence bands as a result of inhibition of the intramolecular charge-transfer process upon binding to these metal ions. The color changes can be easily seen by the naked eye. The binding stoichiometry between this probe and Cu(2+) ions has been determined to be 1:2 by a Job plot of the fluorescence data with a binding constant of ((6.2±0.6)×10(9)) M(-2). The corresponding value for Hg(2+) ions is about sixfold smaller.

Synthesis and in Vitro Photodynamic Activities of Pegylated Distyryl Boron Dipyrromethene Derivatives

A series of pegylated distyryl boron dipyrromethenes have been prepared and characterized. Their in vitro photodynamic activities in Tween 80 emulsions have also been investigated against HT29 human colorectal carcinoma cells. The derivative having five triethylene glycol chains (compound 8) exhibits the highest photocytotoxicity with an IC(50) as low as 7 nM. It is also localized preferentially in the endoplasmic reticulum of the cells and can induce predominately apoptosis upon illumination.

A ratiometric near-infrared pH-responsive fluorescent dye based on distyryl BODIPY

A novel distyryl boron dipyrromethene substituted with two 4-(dimethylamino)phenylethynyl groups at the 2- and 6-positions has been synthesised and characterised. It exhibits remarkable and reversible pH-responsive changes in the absorption and fluorescence emission spectra, both in organic and in aqueous media.