| Cysteine(Cys)plays an important role in regulating many biological processes in humans.Since Cys is involved in a variety of antioxidant activity mechanisms,many diseases are caused by abnormal changes in the level of biological.Therefore,the development of a sensitive,highly selective and less invasive tool for real-time monitoring of Cys could be of great importance and urgency in the early screening and diagnosis of diseases.Near-infrared fluorescence(NIR,650 ～ 900 nm)(NIRF)imaging is widely used to detect small molecules in vivo because of its non-invasive and sensitive advantages.However,NIR fluorescence probes have limited penetration depth,which makes it difficult to image deep tissues in vivo.Photoacoustic imaging(PAI)is a promising new non-invasive biomedical imaging technology that combines the advantages of traditional optical with acoustic imaging,overcomes the limitations of traditional optical imaging,and achieves high spatial resolution imaging of deep tissues in living animals.Therefore,NIRF and PA imaging are expected to achieve non-invasive and accurate detection of deep tissues and provides new methods for early diagnosis and treatment of diseases.In this work we dedicated to investigate the deep penetration depth and rapid response of PA and NIRF dual-modality activatable probes to reveal the role of Cys in mouse disease models.The specific work is as follows:(1)In the second chapter,we use 2-thiophenecarbonyl chloride as a specific recognition group and reaction with thiazolyl to synthesize the probe CER for NIRF imaging.The probe CER is able to specifically recognize Cys and is excited its NIRF signal at 734 nm.We have validated the spectroscopic performance of this newly developed probe that specifically recognizes Cys and can be used for fluorescence imaging to detect Cys levels in biological samples of inflammation models.(2)In Chapter 3,we used acrylate as a Cys-specific recognition group to design and synthesize CGR,a small molecule probe that can be used for PA imaging with CGR activating its PA signal at 730 nm after specific recognition with Cys,which has high sensitivity and rapid response CGR has also been successfully applied to PA imaging of Cys concentration levels in mouse tumor models,providing a new and effective tool for the detection of tumor cancers.(3)In Chapter 4,a novel NIRF/PA bimodal small molecule probe CDR was designed and synthesized for the non-invasive detection of Cys and in vivo diagnosis of liver injury.Probe CDR consists of an acrylate caged NIR quinoline-oxanthene dye.CDR is initially devoid of NIRF and PA signals because it is in a passivated state,which weakens the ability of the oxygen atom to provide electrons.In the presence of Cys,NIRF/PA signal was turned on at725 nm excitation wavelength.Due to the complementary advantages of NIRF/PA imaging,the probe CDR is able to image Cys levels at the site of liver injury with high sensitivity and depth.At the same time,by NIRF/PA imaging,we found the repair effect of NAC(acetylcysteine,a therapeutic drug for liver injury)drug on liver injury.Thus,this dual-mode probe is expected to provide a new approach for the in-depth study,diagnosis and treatment of liver injury. |
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