ABSTRACT
Optoacoustic imaging is a new biomedical imaging technology with clear benefits over traditional optical imaging and ultrasound. While the imaging technology has improved since its initial development, the creation of dedicated contrast agents for optoacoustic imaging has been stagnant. Current exploration of contrast agents has been limited to standard commercial dyes that have already been established in optical imaging applications. While some of these compounds have demonstrated utility in optoacoustic imaging, they are far from optimal and there is a need for contrast agents with tailored optoacoustic properties. The synthesis, encapsulation within tumor targeting silica nanoparticles and applications in in vivo tumor imaging of optoacoustic contrast agents are reported.
Subject(s)
Biosensing Techniques/methods , Nanoparticles/chemistry , Pancreatic Neoplasms/diagnostic imaging , Photoacoustic Techniques/methods , Animals , Carbocyanines/chemistry , Contrast Media/chemical synthesis , Contrast Media/pharmacokinetics , Female , Mice , Silicon Dioxide/chemistryABSTRACT
Squaraine dyes are a class of organic dyes with strong and narrow absorption bands in the near-infrared. Despite high molar absorptivities and fluorescence quantum yields, these dyes have been less explored than other dye scaffolds due to their susceptibility to nucleophilic attack. Recent strategies in probe design including encapsulation, conjugation to biomolecules, and new synthetic modifications have seen squaraine dyes emerging into the forefront of biomedical imaging and other applications. Herein, we provide a concise overview of (1) the synthesis of symmetrical and unsymmetrical squaraine dyes, (2) the relationship between structure and photophysical properties of squaraine dyes, and (3) current applications of squaraine dyes in the literature. Given the recent successes at overcoming the limitations of squaraine dyes, they show high potential in biological imaging, in photodynamic and photothermal therapies, and as molecular sensors.
Subject(s)
Cyclobutanes/chemistry , Fluorescent Dyes/chemistry , Phenols/chemistry , Animals , Chemistry Techniques, Synthetic/methods , Cyclobutanes/chemical synthesis , Cyclobutanes/therapeutic use , Fluorescent Dyes/chemical synthesis , Fluorescent Dyes/therapeutic use , Humans , Optical Imaging/methods , Phenols/chemical synthesis , Phenols/therapeutic use , Photochemotherapy/methods , Photothermal Therapy/methodsABSTRACT
G-Quadruplex DNA has been recognized as a highly appealing target for the development of new selective chemotherapeutics, which could result in markedly reduced toxicity toward normal cells. In particular, the cyanine dyes that bind selectively to G-quadruplex structures without targeting duplex DNA have attracted attention due to their high amenability to structural modifications that allows fine-tuning of their biomolecular interactions. We have previously reported pentamethine and symmetric trimethine cyanines designed to effectively bind G-quadruplexes through end stacking interactions. Herein, we are reporting a second generation of drug candidates, the asymmetric trimethine cyanines. These have been synthesized and evaluated for their quadruplex binding properties. Incorporating a benz[c,d]indolenine heterocyclic unit increased overall quadruplex binding, and elongating the alkyl length increases the quadruplex-to-duplex binding specificity.
Subject(s)
Alkynes/chemistry , Alkynes/pharmacology , G-Quadruplexes/drug effects , Base Sequence , DNA/chemistry , DNA/genetics , Drug Design , Indoles/chemistry , Models, MolecularABSTRACT
Eight near-infrared heptamethine cyanines have been successfully synthesized based on IR 786 with oxygen, sulfur and amine moieties at the central position. These dyes show diverse optical properties resulting from different substitutions. Particularly, the heptamethine dyes with amine moieties have larger Stokes shifts and higher quantum yields of fluorescence. We also investigated these dyes for tumor cell cytotoxicity using cell viability and in vitro proliferation assays. Two of the compounds showed high cytotoxicity against PC-3 cancer cells.
