Liver Injury Long-Term Monitoring And Fluorescent Image-Guided Tumor Surgery Using Self-Assembly Amphiphilic Donor-Acceptor NIR-Ⅱ Dyes

Imaging in the second near-infrared window(NIR-II,1000-1700 nm)has many advantages such as high resolution,sensitivity,non-radiation and low cost,which has been widely investigated in biological imaging research.At present,NIR-II probes including single-walled carbon nanotubes(SWCNT),semiconducting quantum dots(QDs),rare-earth doped nanoparticles(RENPs)and conjugated polymers have been actively explored for biomedical imaging.However,their unfavorable properties such as slow metabolism and high toxicity limit their clinical translation.Therefore,organic small-molecular probes are the most desirable candidates for translation into clinical applications because of their simple and well-defined structure,fast excretion and low toxicity.Most organic small-molecular NIR-II dyes are facing the challenge of low solubility.Modifications of dyes have been usually performed to improve the water solubility,such as amphiphilic polymer encapsulation to form nanoparticles,modification with sulfonic group,and polyethylene glycolation(PEGylation).PEGylated probes usually exhibit excellent properties such as increased solubility and biocompatibility,reduced immunogenicity,prolonged circulation lifetime and passively targeting to solid tumors through the enhanced permeability and retention(EPR)effect.Herein,we report a novel NIR-II fluorescent dye TQT 1009 with asymmetric donor-acceptor(D–A)type core.TQT 1009 reduced molecular weight with attractive optical properties compared with the most of reported D-A-D dyes.The asymmetric structure did not affect the absorption,emission,and quantum yield.Four kinds of PEGs(PEGn K,n = 0.5,2,5,10)were used to conjugate with TQT1009 to construct amphiphilic NIR-II probes.The resulted amphiphilic TQP n K(n = 0.5,2,5,10)selfassembled to form nanoparticles with controllable size and exhibited superhydrophilicity,deep tissue penetration,prolonged circulation time,and high imaging contrast for vessels,bones,intestines,lymph,and tumor in vivo.In particular,TQP 10 K exhibited prolonged blood circulation(> 96 h)and tumor retention time(> 7 d)with high tumor imaging contrast after intravenous injection,which realized liver dysfunction long-term monitoring and extended the time window for image-guided surgery.Overall,TQT 1009 is a novel and promising NIR-II dye with attractive optical properties.Further conjugation with PEGs lead to nanoprobes with favorable properties for bioimaging application.Moreover,our study may lead to new insight of designing asymmetric NIR-II probes for self-assembling and bring a new perspective for longterm monitoring liver injury in small animal models.