Preparation And Performance Study Of Multimodal Imaging Liposomes

The second near-infrared window(NIR-II)fluorescence imaging technology has important applications in vivo imaging and surgical guidance.Combining NIR-II fluorescence imaging with magnetic resonance imaging(MRI)and photoacoustic imaging(PAI)to prepare multimodal imaging nanoparticles,using the advantages of the three imaging modes to overcome the shortcomings of single imaging,can obtain high sensitivity,high resolution and accurate diagnostic information.In this paper,the NIR-II dye IR-1061,NIR-I dye ICG and near-infrared quantum dot u-CuS QDs were co-loaded for the first time using liposome as the carrier.A multifunctional nano-diagnostic agent(IR-1061-ICG-QD-lip)with enhanced near-infrared II(NIR-II)fluorescence,photoacoustic and magnetic resonance trimodal diagnosis and photothermal therapy was constructed.The results showed that the IR-1061-ICG-QD-lip was spherical in shape,uniform in size,and well dispersed,and it was clearly observed that u-CuS QDs was co-loaded into the lipid.The average particle size was 161.1 ± 1.8 nm,the polydispersity coefficient was 0.176,and the zeta potential was 26.5 ± 0.6 mV.IR-1061-ICG-QD-lip had good stability,and there was no significant change in particle size and zeta potential at 7 days after preparation,and no precipitation was observed after 30 days of preparation.Fluorescenceand spectra and fluorescence imaging showed that the co-loading of IR-1061 and ICG significantly increased the intensity of fluorescence signal in NIR-II.The results of photoacoustic and MRI performance studies signed that IR-1061-ICG-QD-lip has good photoacoustic imaging performance and magnetic responsiveness.Cytotoxicity experiments suggested that IR-1061-ICG-QD-lip has a good photothermal therapy effect on tumor cells.And in vivo fluorescence imaging results indicated that IR-1061-ICG-QD-lip has the feasibility of in vivo NIR-II fluorescence imaging.Therefore,the co-load of ICG and IR-1061 can effectively increase the fluorescence intensity of NIR-II and IR-1061-ICG-QD-lip has the potential of NIR-IIfluorescence/photoacoustic/magnetic resonance trimodal imaging and tumor photothermal therapy.On this basis,we further investigated the enhancement of the fluorescence imaging of NIR-II dye by NIR-I dye.The NIR-I fluorescent dye IR-780 and IR-1061 were then co-loaded onto the liposomes by membrane hydration.The fluorescence properties of liposomes were characterized by fluorescence spectroscopyand in vitro fluorescence imaging to investigate the synergistic effect of IR-780 and IR-1061 on the enhancement of NIR-II fluorescence signal.The results showed that IR-780 and IR-1061 co-loaded liposomes(IR-1061-780-lip)significantly enhanced the fluorescence emission of NIR-II,which was verified the feasibility of realizing NIR-II fluorescence signal enhancement by NIR-I fluorescent dye and NIR-II fluorescent dye co-loading.In addition,the in vitro photoacoustic properties of the co-loaded liposomes were tested and found to be linearly related to the IR-1061-780-lip concentration.Cytological evaluation found that IR-1061-780-lip inhibited tumor cells by 50% after continuous laser irradiation for 2 min,indicating that it can be used for photothermal treatment of tumors.Consequently,the co-load of IR-780 and IR-1061 can effectively increase the fluorescence intensity of NIR-II and IR-1061-780-lip has the potential of NIR-II fluorescence/photoacoustic bimodal imaging and tumor photothermal therapy.In this study,a strategy was proposed to synergistically enhance the fluorescence intensity of NIR-II by NIR-I and NIR-II fluorescent dyes,and the feasibility and universality of the method were verified by investigating the fluorescence properties of IR-1061-ICG-QD-lip and IR-1061-780-lip.It provides a new design idea for improving the quality of NIR-II fluorescence imaging.In addition,IR-1061-ICG-QD-lip,which combines fluorescent dyes with ultra-small copper sulfide quantum dots that can be removed by kidneys,can simultaneously achieve NIR-II fluorescence imaging,MRI and PAI multimodal imaging and photothermal therapy,provide more accurate diagnostic information.Preparation of IR-1061-780-lip by simple membrane hydration method,enhanced NIR-II fluorescence imaging / photoacoustic bimodal imaging and photothermal therapy,andIR-1061-780-lip has low toxicity and has broad application prospects in tumor diagnosis and surgical navigation.