Super Bright Near-infrared Ⅱ Fluorophores For Bioimaging And Therapy

Near-infrared(NIR)fluorescence imaging affords high spatial and temporal resolution for in vivo imaging.The NIR-Ⅰ imaging(emission:700-900 nm)shows a relatively low penetration depth for its high autofluorescence and tissue scattering in this range.In comparison,NIR-Ⅱ imaging(emission:1000-1700 nm)offers a deeper penetration for the reduced tissue scattering and autofluorescence,has allowing for transparent in vivo imaging.Currently,the NIR-Ⅱ fluorescent probes include inorganic fluorescent probes,such as quantum dots(QDs),rare earth-based nanomaterials,etc.,and organic fluorescent probes,such as donor-acceptor-donor(D-A-D)dyes and cyanine/polymethine dyes.The inorganic fluorescent probes exhibit high fluorescence quantum yields(QYs)but lack of biosafety,so it is long away from clinical translation.In comparison,the organic fluorophores show high biosafety,biocompatibility,while they possess low fluorescence QYs,and unknow/poor in vivo pharmacokinetics,poor photostability.Moreover,multiple and complex synthetic steps are followed for the synthesis of these fluorophores.Therefore,it is an urgent demand for developing a NIRⅡ probe with high fluorescence QY,high biosafety and decent pharmacokinetics.In this study,we have re developed a series of organic dyes-based NIR-Ⅱ probes with high QY and good in vivo pharmacokinetics.This research We screened studied various cyanine dyes and surfactants,which are the main components.and systematically studied one hundred different formulations of 11 different types of surfactants and 9 cyanine dyes,NIR-Ⅱ probes with high brightness and high stability have been obtained.This compounds have several advantages:(1)They exhibit superhigh NIR-Ⅱ fluorescence enhancement,and high photostability compared with that of cyanine dyes;(2)They show high biological safety due to the high biological safety of both of the components,some of which under clinical setting or have been approved by the Food and Drug Administration(FDA)(e.g.,indocyanine green,ICG);(3)This approach improves the in vivo pharmacokinetics of cyanine dyes;(4)The complexes promote the production of the singlet oxygen which would benefit the photodynamic therapy using this compounds.In this study,four sections have been included:the probes synthesis and in vitro characterization and evaluation of their t properties(i.e.,the optical properties including fluorescence efficiency,brightness,and photostability);Following by this,the pharmacokinetics and in vivo imaging performance of the probes were sy stematically screened.Then,the poor pharmacokinetics of some compounds were optimized with cell membrane coating,such as IR-783@Lecithos and IR-783@Tween 20.Last,the screened probes with the optimal properties were applied in in vivo bioimaging or diseases models.In this study,we established a new platform for enhancing the fluorescence intensity and improving the pharmacokinetics of the organic NIR-Ⅱ dyes.We for the first time systematically studied the in vivo application of surfactants to enhance the fluorescence intensity of cyanine dyes.A series of NIR-Ⅱ fluorescent probes with superhigh fluorescence intensity,improved in vivo pharmacokinetic have been developed.The probes also exhibit a potential for tunable surface modification This study also provides with a fluorescence enhancement strategy for improving a variety of NIR-Ⅱ fluorescent dyes.Moreover,the components used in these compounds show high safety,which in turn greatly accelerates the process of clinical translation of NIRⅡ fluorescence imaging.