| Background:Breast cancer is the most common malignant tumor in women.Early accurate diagnosis is the key to improve the cure rate and improve the quality of life of the patients.The rapid development of imaging,especially molecular imaging,plays a more and more important role in the early diagnosis and treatment effect of this disease.Nanoparticles,as molecular imaging contrast agents,have been developing rapidly in recent years due to their tissue penetrability,high resolution,biocompatibility and versatility.In this study,3 novel molecular imaging contrast agents were developed and applied to multimodal imaging for breast cancer.Objective:To design and build two molecular targeting contrast agents of iron oxide(USPIO@Cy5)and manganese oxide(MnO@IR808)nanoparticles,evaluate its multimodal targeting imaging of breast cancer;and to investigate the choice of nano materials based on two tungsten sulfide nanosheet(WS2)of photoacoustic imaging in diagnosis of breast cancer.Materials and Methods:We assembled amphiphilic polymer DSPE-PEG coupling with targeting Cy5 molecules conjugated to the iron oxide nanoparticles surface by chemical modification form a novel kind of nanomolecular targeting contrast agent that is USPIO@Cy5 for tumor targeting and NIRF/MRI dual modal imaging.We also designed a near-infrared seven methylene cyanine small molecule derivative IR808 functionalized MnO2 magnetic nanoparticles,and applied it to breast cancer targeted MRI,fluorescence and photoacoustic multimodality imaging.This nanomolecular targeting contrast agent is assembled by covalent crosslinking to assemble the IR808 dye onto the surface of magnetic MnO2 nanoparticles wrapped in two amphiphilic polymers.3.Single-layer WS2(S-WS2)and multi-layer WS2(M-WS2)were modified with human serum albumin(HSA),using small animal photoacoustic imaging system to detect the photoacoustic signal intensity correlation to the number of layer of WS2 nanosheets in vitro,and compare the signal intensity between S-WS2 and M-WS2,as well as the effect of photoacoustic imaging in grafted breast cancer;the cell toxicity and biological toxicity of WS2 were also detected in vitro and in vivo,respectively.Results:1.In this study,we have successfully constructed the USPIO@Cy5 nanoparticles with an average size of about 21 nm,The results of in vitro experiments showed that the USPIO@Cy5 can pass through breast cancer cell membrane anion transporter OATPs transmembrane transport into the cell and localized to the mitochondria,as the anion transporter OATPs in breast cancer cells are overexpressing,the Cy5 molecules has a good targeting effect of breast cancer.In vivo imaging experiments show that USPIO@Cy5 nanoparticles have good breast cancer targeting ability,which can obtain good effect of MRI/NIRF dual modal imaging in vivo.2.We have also successfully synthesized the MnO@IR808 nanomolecular targeting contrast agent with an average size of about 40nm.In vitro cell test results showed that MnO@IR808 nanomolecular targeting contrast agent targeted breast cancer cell by IR808 mediated,and located in mitochondria.In vivo animal imaging experimental results showed that MnO@IR808 nanomolecular targeting contrast agent as a highly efficient and stable targeted agent can be specific MRI/NIRF/PA three modal imaging for animal transplantation breast cancer.3.Human serum albumin(HSA)modified WS2 nanosheets can effectively enhance the intensity of photoacoustic imaging signal,and have good biosafety,the less layer WS2 nanoscale with the higher intensity of the photoacoustic signal,and the single-layer WS2 can produce higher signal intensity than multi-layer WS2 on PA imaging of breast cancer.Conclusion:Three novel nanomolecular targeting contrast agents were successfully constructed in this study.The experimental results showed those three kinds of contrast agents have good targeting ability to grafted breast cancer,and provide new ideas and new methods for early detection of breast cancer and assessment of its treatment efficacy... |
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