Application Of Photoacoustic Molecular Imaging In The Targeted Diagnosis And Treatment Of Diseases

Photoacoustic?PA?molecular imaging technology is widely used as a new medical imaging modality for the diagnosis and treatment of diseases because it combines the advantages of high contrast and large penetration depth of PA imaging and the high specificity of molecular imaging.In recent years,PA molecular imaging based on in vivo endogenous molecular probes such as hemoglobin,melanin,etc.can show the high-resolution veins of subcutaneous blood vessels of small animals and the precise location of melanoma.However,for PA molecular imaging of special diseases such as tumors and inflammatory lesions,the light absorption and scattering of endogenous molecules such as hemoglobin and melanin will significantly increase the background noise of imaging and affect the penetration depth of imaging.Therefore,it is urgent to design and synthesize exogenous molecular probes with high specificity and strong near infrared?NIR?absorption.This paper focuses on the design and synthesis of PA molecular probes.The goal is to perform highly sensitive,highly specific,and deep imaging diagnosis of subcutaneous xenografts,deep orthotopic gliomas,and rheumatoid arthritis?RA?.In the first part,we have designed and synthesized a new PA probe based on the highly biocompatible transitional metal dichalcogenides?TMDCs?family member molybdenum selenide?MoSe₂?and FDA-approved indocyanine green?ICG?as the integration of diagnosis and treatment of subcutaneous transplantation tumor PA imaging/photothermal therapy?PTT?nano reagents?sMoSe₂-ICG NSs?.sMoSe₂-ICG NSs have strong absorption at 830 nm,and good photostability and biocompatibility.In vivo and in vitro experiments have shown that sMoSe₂-ICG NSs have excellent PA performance and photothermal conversion ability,can be highly sensitive imaging of breast cancer 4T1 subcutaneously implanted tumors,and real-time track the concentration of nanomaterials in tumors,thereby guiding the efficiency of tumors PTT.The innovation of this work lies in cleverly connecting the ICG to the surface of MoSe₂,which not only increases the NIR absorption of MoSe₂,but also increases the circulation time of ICG in the body,making sMoSe₂-ICG NSs the efficient PA imaging/PTT reagents.In the second part,the first part of the results show that we have successfully achieved a high-specificity,high-sensitivity PA imaging of subcutaneous xenografts.However,high-sensitivity PA imaging of gliomas in situ beneath the skull remains a challenge.We selected MoS₂,another member of the TMDCs family,as a carrier,and after loading ICG,a new nanoprobe?MoS₂-ICG?was formed.Characterization experiment results show that the strongest absorption peak of MoS₂-ICG is located at800 nm,which is within the NIR biological window.The results of the phantom experiment show that,compared with the 675 nm wavelength in the visible region,the800 nm pulsed laser can penetrate the skull well.The results of in vivo experiments further confirmed that MoS₂-ICG entered the mouse through the tail vein at 5 h post injection and its PA signal can be significantly stimulated by 800nm pulsed laser.The PA image shows that the tumor is located 3.5 mm below the skull.This work shows that PA molecular imaging based on NIR molecular probes can perform highly sensitive imaging of large depth lesions.In the third part,RA is a common immune inflammatory disease of bone and joints.Its morbidity is hidden and the cause is unknown.Red swelling and heat pain appear early.With the development of the disease,bone erosion occurs,causing disability finally.The early recognition and treatment of RA is essential to achieve effective treatment.Compared with tumor lesions,RA lesions are rich in blood and inflammatory molecules are distributed around cartilage and bones,which requires higher penetration ability of PA molecular imaging.In recent years,due to its large tissue penetration depth,high signal-to-noise ratio?SNR?and other characteristics,second near infrared?NIR-II?PA molecular imaging?PMI?technology has provided us with an alternative strategy.However,there is still a lack of RA-specific NIR-II molecular probes.Herein,we have designed and synthesized a tocilizumab?TCZ?modified conjugated polymer nanoparticles?TCZ-PNPs?.TCZ-PNPs have a strong NIR-II extinction coefficient,high photostability and biocompatibility.In vivo studies have shown that TCZ-PNPs have excellent targeting capabilities and can effectively and non-invasively diagnose RA joint tissues with 35.8 dB high SNR in 3D PA tomography images.It is worth noting that the one-month treatment and PA monitoring using TCZ-PNPs showed that RA was significantly inhibited.The results of PA diagnosis and treatment were consistent with clinical Micro-CT and histological analysis results.This work proves that the NIR-II PA molecular imaging technology can image RA lesions in complex tissue environments with high specificity and high SNR.Combining the above three research works,we have successfully achieved the technological improvement from passive target probe synthesis to high targeted probe synthesis and from NIR-I probe design to NIR-II probe design,and the spatial span of high-sensitivity and high SNR imaging from low depth lesions to large depth lesions.These results well demonstrated the advantages of PA molecular imaging technology compared with other optical imaging technologies for accurate diagnosis of different tissue depths and background lesions.