Design And Application Of Polymer Modified Double Rare Earth Doped Carbon Dots Multi-modal Imaging Probe

As a new type of fluorescent carbon nanomaterial,carbon dots are widely used in bioimaging because of their superior performance.However,biological imaging of carbon dots?CDs?is mostly single-modal or dual-modal imaging.Therefore,preparation more efficient multimodal imaging probes with accurate real-time diagnosis and deep understanding of probe metabolism and its distribution in organisms,have become a great challenge in the research of carbon dots.Based on those,to fabricate more suitable MRI/CT/FI trimodal imaging probe,fluorescent CDs were selected as the matrix,Gd³⁺and Yb³⁺as clinical T₁-MRI contrast agent and CT contrast agent,respectively.Herein,two novel multifunctional CDs were constructed by one-step hydrothermal method,and their fluorescence properties and stability in different media and different pH values were explored and their application in MR/CT/FI multimodal imaging was studied.This research content mainly includes the following two parts:1.In this paper,Gd³⁺and Yb³⁺doped fluorescent carbon dots?Gd/Yb@CDs?were prepared by a simple hydrothermal method using Na₂EDTA as carbon source and L-arginine as surface passivation agent.The morphology and composition of fluorescent carbon dots were characterized by transmission electron microscope?TEM?,laser particle size analyzer?Nano ZS?,Fourier transform infrared spectroscopy?FT-IR?,X-ray photoelectron spectroscopy?XPS?and fluorescence spectroscopy.These results showed that the prepared Gd/Yb@CDs had an average particle size of 5.26±0.93 nm and good monodispersity.CDs exhibited excitation-dependent fluorescence emission behavior.The maximum fluorescence emission intensity was obtained at 418 nm when the sample was excited at 340 nm,and fluorescence quantum yield was 16.84%.MTT,tissue section and mouse body weight analysis showed that fluorescent CDs had good biocompatibility.In vitro imaging performance studies had demonstrated that Gd/Yb@CDs had excellent longitudinal relaxation efficiency(r₁=6.65 mM^-1 s^-1)and significant X-ray absorption performance(45.42 HU L g^-1).HeLa cell imaging experiments showed that Gd/Yb@CDs could achieve cell fluorescence imaging through the cell membrane.In vivo MRI/CT imaging demonstrated that this potential MRI/CT/FI multimodality imaging probe could be used for tumor detection.2.PEG,as a hydrophilic polymer,has the advantages of non-toxic,good biocompatibility and low immunogenicity in the body.Therefore,PEG is often applied to modificate biomaterial surfaces.Herein,polyethylene glycol-modified double rare earth doped carbon dots?Gd/Yb@CD@PEG?with ultra-small,uniform particle size of 2.9±0.6nm by a simple hydrothermal method.Fluorescence spectroscopy results showed that Gd/Yb@CDs-PEG had emission-dependent emission characteristics.When the excitation wavelength was 320³90 nm,the emission wavelength was 405⁴65 nm.At the same time,Gd/Yb@CD-PEG showed pH-dependent fluorescence properties,which demonstrated that polymer-modified carbon dots had acidic and basic sites.These CDs were incubated with HeLa for up to 24 h at a concentration of 2 mg m L^-1,and the viability rate of cells was still as high as 90.0%or more,which demonstrated its low cytotoxicity.Cell imaging results revealed that cells not only remained their intact morphology,but also exhibited blue fluorescence,which further proved that Gd/Yb@CD-PEG had promising applications in bioimaging.