A major restriction on optical imaging techniques is the range of available fluorophores that are compatible with aqueous media without aggregation, absorb light above 750 nm with high extinction coefficients, fluoresce with relatively high quantum yields, and resist photodecomposition. Indocyanine green (ICG or A in this paper) is an important example of a fluorophore that fits this description. Other dyes that are becoming increasingly prevalent are select heptamethine cyanine dyes (Cy7) which feature a cyclohexyl framework to rigidify the conjugated alkenes, and meso -chlorine substitution; MHI-148 ( B ) is one example. Methods : Research described here was initiated to uncover the consequences of a simple isoelectronic substitution to MHI-148 that replaces a cyclohexyl methylene with a dialkyl ammonium fragment. Solubility experiments were carried out in aqueous and cell culture media, photophysical properties including fluorescence quantum yields, brightness and stability were measured. Moreover, in vivo pharmacokinetics, distribution and tumor seeking properties were also explored. Results : Modification to incorporate dialkyl ammonium fragment leads to a brighter, more photostable fluorophore, with a decreased tendency to aggregation, complementary solubility characteristics, and a lower cytotoxicity. Conclusion : All the above-mentioned parameters are favorable for many anticipated applications of the new dye we now call quaternary cyanine-7 or QuatCy .
The ability of brain tissue to regenerate is limited; therefore, brain diseases (i.e., trauma, stroke, tumors) often lead to irreversible motor and cognitive impairments. Therapeutic interventions using various types of injectable biomaterials have been investigated to promote endogenous neural differentiation. Despite promising results in pre-clinical studies, the translation of regenerative medicine to the clinic has many challenges due to the lack of reliable imaging systems to achieve accurate evaluation of the treatment efficacy. Methods : In this study, we developed a dual-channel fluorescence imaging technique to simultaneously monitor tissue ingrowth and scaffold disintegration. Enzymatically crosslinked gelatin-hyaluronic acid hydrogel was labeled with 800 nm fluorophore, ZW800-3a, while the regenerated tissue was highlighted with 700 nm brain-specific contrast agent, Ox1. Results : Using the multichannel fluorescence imaging system, tissue growth and degradation of the NIR hydrogel were simultaneously imaged in the brain of mice. Images were further analyzed and reconstructed to show both visual and quantitative information of each stage of a therapeutic period. Conclusion : Dual-channel in vivo imaging systems can provide highly accurate visual and quantitative information of the brain tissue ingrowth for the evaluation of the therapeutic effect of NIR hydrogel through a simple and fast operating procedure.
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