Aminocyanine Dye Research Articles

A nitroreductase-activatable near-infrared theranostic photosensitizer for photodynamic therapy under mild hypoxia.

In this study, a near-infrared (NIR) theranostic photosensitizer was developed based on a heptamethine aminocyanine dye with a long-lived triplet state. This theranostic molecule can be activated by nitroreductase under mild hypoxia to be used in fluorescence imaging and highly efficient photodynamic therapy (PDT) both in 2D and 3D (spheroids) HeLa cell culture models.

NIR-Fluorescent Multidye Silica Nanoparticles with Large Stokes Shifts for Versatile Biosensing Applications.

We have synthesized and characterized of a series of single and multidye copolymerized nanoparticles with large to very large Stokes shifts (100 to 255nm) for versatile applications as standalone or multiplexed probes in biological matrices. Nanoparticles were prepared via the Stöber method and covalently copolymerized with various combinations of three dyes, including one novel aminocyanine dye. Covalently encapsulated dyes exhibited no significant leakage from the nanoparticle matrix after more than 200days of storage in ethanol. Across multiple batches of nanoparticles with varying dye content, the average yields and average radii were found to be highly reproducible. Furthermore, the batch to batch variability in the relative amounts of dye incorporated was small (relative standard deviations <2.3%). Quantum yields of dye copolymerized nanoparticles were increased 50% to 1000% relative to those of their respective dye-silane conjugates, and fluorescence intensities were enhanced by approximately three orders of magnitude. Prepared nanoparticles were surface modified with polyethylene glycol and biotin and bound to streptavidin microspheres as a proof of concept. Under single wavelength excitation, microsphere-bound nanoparticles displayed readily distinguishable fluorescence signals at three different emission wavelengths, indicating their potential applications to multicolor sensing. Furthermore, nanoparticles modified with polyethylene glycol and biotin demonstrated hematoprotective qualities and reduced nonspecific binding of serum proteins, indicating their potential suitability to in vivo imaging applications.

A near-infrared heptamethine aminocyanine dye with a long-lived excited triplet state for photodynamic therapy.

A water-soluble near-infrared aminocyanine dye has been developed with a long triplet-state lifetime (τ = 9.16 μs in deaerated ethanol). Thereby, extremely high singlet oxygen quantum yield (ΦΔ = 0.20) and low dark cytotoxicity (IC50 = 715.4 μM) were achieved. The potential of the dye as a PDT photosensitizer was demonstrated.

Fine-tailoring the linker of near-infrared fluorescence probes for nitroreductase imaging in hypoxic tumor cells

Imaging hypoxia using fluorescence probes for nitroreductase (NTR) have attracted much attention in last decade. At least three different linkers have been commonly used to connect the recognition unit and reporting unit in reported probes for NTR. Meanwhile, the linker is known to be a key factor for achieving best sensing performance. In this work, three near-infrared fluorescence probes CyNP-1, CyNP-2 and CyNP-3 were designed and synthesized from an aminocyanine dye CyNP. The three probes have the same recognition unit and same fluorescence reporting unit, but different linkers. CyNP-1 was found to have the best sensing performance for NTR with 40-fold of fluorescence enhancement. It is well investigated how the difference of the linkers brings out the different sensing performance by HPLC, MS and docking calculations. In the end, CyNP-1 was found to have good selectivity for NTR and used to imaging hypoxia in Hela cells.

The ratiometric dual-fluorescence of near infrared absorbing aminocyanine dyes: A mechanistic study

A systematic spectral analysis is presented for a heptaaminocyanine dye (Cy7-NCY) and pentaaminocyanine dye (Cy5-NHY). The dyes displayed near infrared and ratiometric dual-fluorescence in viscous environments. Computational studies on these dyes revealed the origin of dual-fluorescence and the nature of the difference in viscous-sensitivity for these dyes. In low-viscous solvents, the amino group can be described as a rotor and was decoupled with the polymethine chain by photo-excitation, displaying an emission peak with long wavelength. In high-viscous solutions, on the contrary, the amino group is almost parallel to the parent polymethine chain and the lone-pair of the amino group is in an appropriate orientation for efficient overlap with the polymethine chain, resulting in an emission peak with short wavelength. The overall balance of the rotating ability for the substituted amino group and the polymethine chain affects the competition between radiative and non-radiative transition processes in a viscous environment.

Improving the brightness and photostability of NIR fluorescent silica nanoparticles through rational fine-tuning of the covalent encapsulation methods.

Near-infrared (NIR) fluorescence imaging technology calls for highly bright and photostable emissive materials for long-term and real-time bioimaging and medical diagnosis. Herein, we report that four aminocyanine dyes were covalently encapsulated inside silica nanoparticles by reverse microemulsion using different linkage methods. The fluorescence brightness and photostability of the obtained fluorescent silica nanoparticles (FSNPs) were found to have direct correlation with the used covalent encapsulation methods, especially the number of anchoring sites of the encapsulated dyes. The aminocyanine dye 4-Si contains three anchoring sites for embedding into the silica nanoparticles, and provides FSNP-4- the FSNP with the best brightness and photostability.

PH-responsive amphiphilic block copolymer prodrug conjugated near infrared fluorescence probe

A novel amphiphilic multi-block copolymer conjugated with both a near infrared fluorescence probe and drug has been designed and prepared by means of ring-opening polymerization (ROP) of N-Carboxy Anhydride (NCA) monomers following a Reversible Addition-Fragmentation Chain Transfer (RAFT) polymerization. At first, an amino group-containing RAFT agent was synthesized and it served as an initiator for the sequential ROP of aspartic acid β-benzyl ester N-carboxy anhydride (Asp-NCA) and e-carbobenzoxy-L-lysine NCA (ZLLys-NCA). Then the multi-block copolymer was prepared by a succeeding RAFT polymerization of poly(ethylene glycol) methyl ether acrylate (OGEA). At the end, both anticancer drug doxorubicin and hydrophobic aminocyanine dye were chemical conjugated to the block copolymer via a hydrazone or amide bond, respectively. The obtained NIRF copolymer and its micelles were characterized by nuclear magnetic resonance (NMR), gel permeation chromatography (GPC), dynamic light scattering (DLS), and UV-vis and fluorescence spectrophotometry. The prodrug has strong fluorescence in the near infrared region and shows pH-responsive drug release behavior, and it has potential application in the theranostics of cancer.

Near-infrared aminocyanine dyes: synthesis, optical properties, and application to the preparation of fluorescent microspheres

Several near-infrared (NIR) fluorescent dyes based on aminocyanine have been designed, synthesized, and used for preparation of NIR fluorescent microspheres. Their spectral properties and pH-dependent optical characteristics were investigated. It was found that different substitution at the central position of the dyes led to diverse optical properties, with especially large effects on their spectroscopic properties. Spectroscopic responses of the fluorescent dyes to changes of pH were different. Under acidic conditions, the wavelengths of maximum absorption of the N-substituted cyanine dyes were clearly red shifted. Dyes with an N-substituted piperazidine ring were the most sensitive. The fluorescent microspheres retained the properties of the parent dyes, making them suitable for applications in biological studies.

Synthesis of polypeptide conjugated with near infrared fluorescence probe and doxorubicin for pH-responsive and image-guided drug delivery

A near infrared fluorescent polymeric drug delivery system (NIRF DDS) with pH-responsive drug release properties has been designed and developed. This material was prepared by chemical conjugation of the anticancer drug doxorubicin and hydrophobic aminocyanine dye to triblock copolypeptide via hydrazone and amide bonds, respectively. Conjugation with aminocyanine shows almost no toxicity of the material, while conjugation with doxorubicin induces pronounced toxicity on the original biocompatible material. The pH sensitive drug release nature of the near infrared fluorescent polymeric drug (NIRF prodrug) was confirmed by accelerated drug release at pH of 5.0 via an in vitro drug release experiment and gradual drug cleavage from the NIRF prodrug during a confocal laser scanning microscopic (CLSM) experiment. The CLSM experiment also reveals that the released drug subsequently migrated to the nucleus, while the polymeric residue still remained in cytoplasm, indicating that the as-prepared polymer can be a promising candidate for theranosis of cancer.

Inside Cover: Combining Aminocyanine Dyes with Polyamide Dendrons: A Promising Strategy for Imaging in the Near‐Infrared Region (Chem. Eur. J. 13/2011)

Inside Cover: Combining Aminocyanine Dyes with Polyamide Dendrons: A Promising Strategy for Imaging in the Near‐Infrared Region (Chem. Eur. J. 13/2011)

Combining Aminocyanine Dyes with Polyamide Dendrons: A Promising Strategy for Imaging in the Near‐Infrared Region

Cyanine dyes are known for their fluorescence in the near-IR (NIR) region, which is desirable for biological applications. We report the synthesis of a series of aminocyanine dyes containing terminal functional groups such as acid, azide, and cyclooctyne groups for further functionalization through, for example, click chemistry. These aminocyanine dyes can be attached to polyfunctional dendrons by copper-catalyzed azide alkyne cycloaddition (CuAAC), strain-promoted azide alkyne cycloaddition (SPAAC), peptide coupling, or direct S(NR)1 reactions. The resulting dendron-dye conjugates were obtained in high yields and displayed high chemical stability and photostability. The optical properties of the new compounds were studied by UV/Vis and fluorescence spectroscopy. All compounds show large Stokes shifts and strong fluorescence in the NIR region with high quantum yields, which are optimal properties for in vivo optical imaging.