Cyanine Research Articles

Light in a Heartbeat: Bond Scission by a Single Photon above 800 nm.

Photocages enable scientists to take full control over the activity of molecules using light as a biocompatible stimulus. Their emerging applications in photoactivated therapies call for efficient uncaging in the near-infrared (NIR) window, which represents a fundamental challenge. Here, we report synthetically accessible cyanine photocages that liberate alcohol, phenol, amine, and thiol payloads upon irradiation with NIR light up to 820 nm in aqueous media. The photocages display a unique chameleon-like behavior and operate via two distinct uncaging mechanisms: photooxidation and heterolytic bond cleavage. The latter process constitutes the first example of a direct bond scission by a single photon ever observed in cyanine dyes or at wavelengths exceeding 800 nm. Modulation of the beating rates of human cardiomyocytes that we achieved by light-actuated release of adrenergic agonist etilefrine at submicromolar concentrations and low NIR light doses (∼12 J cm-2) highlights the potential of these photocages in biology and medicine.

Rotor-based image-guided therapy of glioblastoma

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an “extended conjugation & molecular rotor” strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the “extended conjugation & molecular rotor” strategy can be used to guide the design of other photothermal agents.

Phototruncation cell tracking with near-infrared photoimmunotherapy using heptamethine cyanine dye to visualise migratory dynamics of immune cells

Noninvasive invivo cell tracking is valuable in understanding the mechanisms that enhance anti-cancer immunity. We have recently developed a new method called phototruncation-assisted cell tracking (PACT), that uses photoconvertible cell tracking technology to detect invivo cell migration. This method has the advantages of not requiring genetic engineering of cells and employing tissue-penetrant near-infrared light. We applied PACT to monitor the migration of immune cells between a tumour and its tumour-draining lymph node (TDLN) after near-infrared photoimmunotherapy (NIR-PIT). PACT showed a significant increase in the migration of dendritic cells (DCs) and macrophages from the tumour to the TDLN immediately after NIR-PIT. This migration by NIR-PIT was abrogated by inhibiting the sphingosine-1-phosphate pathway or Gαi signaling. These results were corroborated by intranodal immune cell profiles at two days post-treatment; NIR-PIT significantly induced DC maturation and increased and activated the CD8+ T cell population in the TDLN. Furthermore, PACT revealed that NIR-PIT significantly enhanced the migration of CD8+ T cells from the TDLN to the tumour four days post-treatment, which was consistent with the immunohistochemical assessment of tumour-infiltrating lymphocytes and tumour regression. Immune cells dramatically migrated between the tumour and TDLN following NIR-PIT, indicating its potential as an immune-stimulating therapy. Also, PACT is potentially applicable to a wide range of immunological research. This work was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Centre for Cancer Research (grant number: ZIA BC011513 and ZIA BC011506).

Surface exciton polariton enhanced Goos-Hänchen and Imbert-Fedorov shifts and their applications in refractive index sensing.

The spatial and angular Goos-Hänchen shifts (GHSs) and Imbert-Fedorov shifts (IFSs) are theoretically investigated in a modified Kretschmann-Raether configuration consisting of glass prism, J-aggregate cyanine dye, and air. With the excitation of surface excitation polaritons (SEPs), the spatial and angular GHSs and IFSs for the transverse magnetic polarized light are strongly enhanced around the resonant angle of SEP. A highly sensitive gas sensor based on the SEP enhanced GHS (or IFS) is proposed, which exhibits the refractive index sensitivity on the order of 106λ/RIU (or 105λ/RIU) (λ: illumination wavelength; RIU: refractive index unit) for the GHS- (or IFS-) based gas sensor, respectively.

Optimizing cyanine dye properties for enhanced dyeing and inkjet printing on diverse Substrates: Photophysical and colorimetric investigations

Cyanine-based cationic dyes with different substituents in the donor unit were easily synthesized using readily available starting materials. The prepared dye molecules were spectroscopically characterized by NMR, FT-IR, and HR-Mass, and their thermal stability was measured by TGA, DSC, and XRD. Based on the TGA and DSC measurements, it was concluded that all the dyes are thermally stable up to 200 °C. Also, powder XRD was studied for all dyes to identify the explicit crystallinity and morphological nature of the dyes. A dye dispersion solution was prepared for the proper dyeing of modacrylic fabric and the dyed fabric showed good color strength K/S for dyes R1, R2, and R6 and fragile color strength for R3, R4,and R5. These dyes are also used for printing on substrates like paper and fabric using ink-jet printing. These dyes were also used for transferability printing applications on various fabrics.

Coumarin Linked Cyanine Dye for the Selective Detection of Cyanide Ion in Environmental Water Sample.

A benzoxazole-coumarin-based probe BOC, was synthesized and validated for its anion sensing ability and found to be effective in recognizing cyanide ions. Upon addition of cyanide, a spontaneous color change was observed that was visible to the naked eye. The sensitization process takes place with nucleophilic addition, and the cyanide ion added to the probe disrupts the intra molecular charge transfer transition (ICT) between the donor and acceptor units, causing the pink colored probe to become yellow. Ultraviolet and fluorescence methods were applied to measure the detection limits of probes with added cyanide ions, which were found to be 3.47 µM and 2.48 nM. The stoichiometry of the probe with the cyanide ion was determined by the Job's method, NMR titration, and mass spectrometry and was found to be in a 1:1 ratio. The results obtained from the visual and UV-visible spectral studies are justified by theoretical calculations. The cyanide-loaded probe induced visual changes, which enabled the development of a test strip for field application, and the prepared strip can be used to detect the ppm level of cyanide in water samples. The developed probe, BOC, can be used to detect cyanide ions in various water samples.

Structure–Properties Correlations in the Range of Cationic Spiropyrans as Analogues of Cyanine Dyes

AbstractRecently the need for smart materials has been extremely growing, and the development of materials with appropriate characteristics has become one of the main challenges. Heptamethine cyanine dyes are widely used in theranostics and photovoltaics due to their remarkable optical properties. However, they are characterized by “rigid” non–changable properties. The main aim of the current study is to unveil correlation between structure and optical properties in the range of vinyl‐3H‐indolium substituted spiropyrans, which can be considered as the closest analogs of heptamethine cyanines with the photocontrolable optical and fluorescent properties. The effects of substitution in indoline and 2H‐chromene cycles, as well as anion change are under the study. To achieve this goal, a series of spiropyran iodides and perchlorates with methyl, methoxy substituents or fluorine atom in position 6′, as well as a conjugated vinyl‐3H‐indolium fragment in position 8′, were synthesized. The structure of the compounds was carefully studied using SC XRD, NMR, IR and mass spectroscopy. Then, studies on absorption and photoluminescence characteristics, as well as photochromic behavior were carried out.

Molecular Dynamics Study of The Lysozyme-Based Drug Delivery Nanosystems Loaded with Antiviral Drugs and Cyanine Dyes

Molecular Dynamics Study of The Lysozyme-Based Drug Delivery Nanosystems Loaded with Antiviral Drugs and Cyanine Dyes

Fluorogenic Monomethine Cyanine Dyes for Nucleolar RNA Imaging in Living Cells

Fluorogenic Monomethine Cyanine Dyes for Nucleolar RNA Imaging in Living Cells

Phosphonated Heptamethine Dye Alleviates Radiation‐Induced Bone Loss

AbstractHigh levels of reactive oxygen species (ROS) are closely associated with osteoclast formation and function, resulting in bone loss. Herein, a novel ROS scavenger, named IR‐ALN, based on the heptamethine cyanine (Cy7) dyes is reported. IR‐ALN not only retains the inherent near‐infrared (NIR) fluorescence imaging and ROS scavenging activity of Cy7 dyes, but is also selectively absorbed by the osteoclast precursor cells, inhibiting osteoclast differentiation and bone resorption activity. Moreover, IR‐ALN exhibits bone‐targeted accumulation in a dose‐dependent manner and effectively alleviates bone and trabecular volume loss caused by X‐ray. The results suggest that IR‐ALN is a potential radioprotective agent that prevents radiation‐induced bone loss. Furthermore, the design strategy for IR‐ALN can be used as a reference for the development of new radioprotective agents.

Fine-tuning of highly bright benzo[c,d]indole-oxazolopyridine cyanine dye for nucleolar RNA imaging in living cells

Here we report on fine-tuning of highly bright fluorogenic cyanine dye, benzo[c,d]indole-oxazolo[5,4-c]pyridine (BIOP: λem = 570 nm, Φfree = 0.00038, Φbound = 0.52), recently developed by our group for nucleolar RNA imaging in living cells. We tuned an emission maximum to the longer wavelength by replacing oxazolopyridine unit with its isomer. The resulting probe with oxazolo[4,5-b]pyridine, named BIOP [4,5-b], exhibited a significant off-on signaling ability for RNA (λem = 580 nm, Φfree = 0.002, Φbound = 0.46) that almost compared with BIOP. BIOP [4,5-b] was applicable to live-cell imaging, where wash-free protocol was available. Importantly, the slight change in spectral features would be expected to minimize the false signal from BIOP [4,5-b] in co-staining experiments with typical green-emissive dyes. In addition, thanks to the unique spectral shape that is typical of cyanine dyes, we demonstrate that yellow-emissive BIOP [4,5-b] also did work as a pseudo red-emissive dye (λem > 600 nm) for live-cell RNA imaging, for which we just switch filter set to typical one for real red-emissive dyes (Ex 560/40 nm; Em 645/75 nm).

A Modular Approach for the Synthesis of Diverse Heterobifunctional Cyanine Dyes.

Herein, we present a straightforward synthetic route for the design and synthesis of diverse heterobifunctional cyanine 5 dyes. We optimized the workup by harnessing the pH- and functional group-dependent solubility of the asymmetric cyanine 5 dyes. Therefore, purification through chromatography is deferred until the last synthesis step. Demonstrating successful large-scale synthesis, our modular approach prevents functional group degradation by introducing them in the last synthesis step. These modifiable heterobifunctional dyes offer significant utility in advancing biological studies.

DNA Framework-Engineered Assembly of Cyanine Dyes for Structural Identification of Nucleic Acids.

DNA nanostructures serve as precise templates for organizing organic dyes, enabling the creation of programmable artificial photonic systems with efficient light-harvesting and energy transfer capabilities. However, regulating the organization of organic dyes on DNA frameworks remains a great challenge. In this study, we investigated the factors influencing the self-assembly behavior of cyanine dye K21 on DNA frameworks. We observed that K21 exhibited diverse assembly modes, including monomers, H-aggregates, J-aggregates, and excimers, when combined with DNA frameworks. By manipulating conditions such as the ion concentration, dye concentration, and structure of DNA frameworks, we successfully achieved precise control over the assembly modes of K21. Leveraging K21's microenvironment-sensitive fluorescence properties on DNA nanostructures, we successfully discriminated between the chirality and topology structures of physiologically relevant G-quadruplexes. This study provides valuable insights into the factors influencing the dynamic assembly behavior of organic dyes on DNA framework nanostructures, offering new perspectives for constructing functional supramolecular aggregates and identifying DNA secondary structures.

Devastating the Supply Wagons: Multifaceted Liposomes Capable of Exhausting Tumor to Death via Triple Energy Depletion.

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

Cy5 Dye Cassettes Exhibit Through-Bond Energy Transfer and Enable Ratiometric Fluorescence Sensing.

The chemosensor literature contains many reports of fluorescence sensing using polyaromatic hydrocarbon fluorophores such as pyrene, tetraphenylethylene, or polyaryl(ethynylene), where the fluorophore is excited with ultraviolet light (<400 nm) and emits in the visible region of 400-500 nm. There is a need for general methods that convert these "turn-on" hydrocarbon fluorescent sensors into ratiometric sensing paradigms. One simple strategy is to mix the responsive hydrocarbon sensor with a second non-responsive dye that is excited by ultraviolet light but emits at a distinctly longer wavelength and thus acts as a reference signal. Five new cyanine dye cassettes were created by covalently attaching a pyrene, tetraphenylethylene, or biphenyl(ethynylene) component as the ultraviolet-absorbing energy donor directly to the pentamethine chain of a deep-red cyanine (Cy5) energy acceptor. Fluorescence emission studies showed that these Cy5-cassettes exhibited large pseudo-Stokes shifts and high through-bond energy transfer efficiencies upon excitation with ultraviolet light. Practical potential was demonstrated with two examples of ratiometric fluorescence sensing using a single ultraviolet excitation wavelength. One example mixed a Cy5-cassette with a pyrene-based fluorescent indicator that responded to changes in Cu2+ concentration, and the other example mixed a Cy5-cassette with the fluorescent pH sensing dye, pyranine.

Orientational effects in the polarized absorption spectra of molecular aggregates.

We present a detailed theoretical analysis of polarized absorption spectra and linear dichroism of cyanine dye aggregates whose unit cells contain two molecules. The studied threadlike ordered system with a molecular exciton delocalized along its axis can be treated as two chains of conventional molecular aggregates, rotated relative to each other at a certain angle around the aggregate axis. Our approach is based on the general formulas for the effective cross section of light absorption by a molecular aggregate and key points of the molecular exciton theory. We have developed a self-consistent theory for describing the orientational effects in the absorption and dichroic spectra of such supramolecular structures with nonplanar unit cell. It is shown that the spectral behavior of such systems exhibits considerable distinctions from that of conventional cyanine dye aggregates. They consist in the strong dependence of the relative intensities of the J- and H-type spectral bands of the aggregate with a nonplanar unit cell on the angles determining the mutual orientations of the transition dipole moments of constituting molecules and the aggregate axis as well as on the polarization direction of incident light. The derived formulas are reduced to the well-known analytical expressions in the particular case of aggregates with one molecule in the unit cell. The calculations performed within the framework of our excitonic theory combined with available vibronic theory allow us to quite reasonably explain the experimental data for the pseudoisocyanine bromide dye aggregate.

Functionalizing TiO2 Nanoparticles with Fluorescent Cyanine Dye for Photodynamic Therapy and Bioimaging: A DFT and TDDFT Study

Functionalizing TiO₂ Nanoparticles with Fluorescent Cyanine Dye for Photodynamic Therapy and Bioimaging: A DFT and TDDFT Study

Polydopamine nanoplatform with near infrared light and pH dual stimuli-responsive for chemo-photothermal cancer therapy.

Photothermal agent accompanying with thermally responsive materials, displays well controlled drug release property, which is well-received as an outstanding design strategy for simultaneous photothermal/chemotherapy in cancer. Cyanine dye, as the prestigious photothermal agent has shown great potential due to its preeminent near-infrared absorbance and excellent thermal conversion efficiency. However, their inherent defect such as inferior photothermal stability, high leakage risk and poor therapy efficacy limit their further application in cancer therapy. Hence, a facile and universal strategy to make up these deficiencies is developed. Chemotherapeutic drug DOX and cyanine dye were loaded into polydopamine (PDA) nanoparticles. The PDA encapsulation dramatically improved the photothermal stability of cyanine dye. Attributed by the PDA structure feature, the thermo-sensitive small molecule glyamine (Gla) is introduced into the PDA surface to lessen leakage. The Gla can form a dense encapsulation layer on the dopamine surface through hydrogen bond. This newly fabricated Cyanine/DOX@PDA-Gla nanopaltform is characterized with NIR light/pH dual-responsive property, high NIR photothermal conversion performance and fluorescence guided chemo-photothermal therapy.

Different Valence States of Copper Ion Delivery against Triple-Negative Breast Cancer.

Different valence states of copper (Cu) ions are involved in complicated redox reactions in vivo, which are closely related to tumor proliferation and death pathways, such as cuproptosis and chemodynamic therapy (CDT). Cu ion mediated Fenton-like reagents induced tumor cell death which presents compelling attention for the CDT of tumors. However, the superiority of different valence states of Cu ions in the antitumor effect is unknown. In this study, we investigated different valence states of Cu ions in modulating tumor cell death by Cu-chelated cyanine dye against triple-negative breast cancer. The cuprous ion (Cu+) and copper ion (Cu2+) were chelated with four nitrogen atoms of dipicolylethylenediamine-modified cyanine for the construction of Cu+ and Cu2+ chelated cyanine dyes (denoted as CC1 and CC2, respectively). Upon 660 nm laser irradiation, the CC1 or CC2 can generate reactive oxygen species, which could disrupt the cyanine structure, achieving the rapid release of Cu ions and initiating the Fenton-like reaction for CDT. Compared with Cu2+-based Fenton-like reagent, the CC1 with Cu+ exhibited a better therapeutic outcome for the tumor due to there being no need for a reduction by glutathione and a shorter route to generate more hydroxyl radicals. Our findings suggest the precision delivery of Cu+ could achieve highly efficient antitumor therapy.

Near-atomic-resolution structure of J-aggregated helical light-harvesting nanotubes.

Cryo-electron microscopy has delivered a resolution revolution for biological self-assemblies, yet only a handful of structures have been solved for synthetic supramolecular materials. Particularly for chromophore supramolecular aggregates, high-resolution structures are necessary for understanding and modulating the long-range excitonic coupling. Here, we present a 3.3 Å structure of prototypical biomimetic light-harvesting nanotubes derived from an amphiphilic cyanine dye (C8S3-Cl). Helical 3D reconstruction directly visualizes the chromophore packing that controls the excitonic properties. Our structure clearly shows a brick layer arrangement, revising the previously hypothesized herringbone arrangement. Furthermore, we identify a new non-biological supramolecular motif-interlocking sulfonates-that may be responsible for the slip-stacked packing and J-aggregate nature of the light-harvesting nanotubes. This work shows how independently obtained native-state structures complement photophysical measurements and will enable accurate understanding of (excitonic) structure-function properties, informing materials design for light-harvesting chromophore aggregates.