The Synthesis Of Water-soluble And NIR-absorptive Perylene Bisimides And Their Applications In Photoacoustic Imaging

In recent years,photoacoustic imaging with the near infrared absorption which has the characteristics of high contrast,high resolution and high penetrability has been widely concerned.However traditional photoacoustic imaging contrast agents such as inorganic gold nanoparticles and organic small molecule dyes with the drawback of high toxicity or synt hetic difficulties have restricted the development of photoacoustic imaging.Perylene bisimide and its derivatives(PDIs)used as a kind of organic semiconducting materials with the advantages of stab le properties of light,heat and chemical,excellent optical performance and easy modification has been widely used in the field of Biology.After obtaining the water-soluble PDIs,regulating its absorption spectrum to near infrared region and using the π-π stacking of perylene core,perylene bisimide can be used as a performance photoacoustic imaging contrast agent.Hence,we prepare two new contrast agents on the basis of perylene bisimide.One is to hybrid perylene bisimide with iron oxide to form a dual-modal photoacoustic/MR imaging agent.Another one is to use sulfo-SMCC to combine perylene bisimide with polypeptide c RGD to synthesis a new photoacoustic imaging contrast agent which has the ability to target early thrombosis.(1)Design and synthesis a dual-modal photoacoustic/MR imaging contrast agent(APPA-Fe3O4@PDI-PEG500-PMAA)by hybriding perylene bisimide with iron oxide.We study the photophysical properties,dispersity and structural stability of it.The results show that APPA-Fe3O4@PDI-PEG500-PMAA has good water solubility and a broad and strong absorption in the near infrared region due to the red shift of the spectra caused by the π-π stacking.The contrast agent can form with an average size of 48 nm which can accumulated in the tumor cell by EPR effect.The morphology of APPA-Fe3O4@PDI-PEG500-PMAA after 24 hours in serum remains the same showing good stability of it.(2)Study the biological characterization of APPA-Fe3O4@PDI-PEG500-PMAA.The properties of photoacoustic imaging,magnetic resonance imaging and photothermal were investigated.88% of the Hela cells survived after co-cultured with the contrast agent at a concentration of 1 mg/mL for 24 hours shows a small cytotoxicity.Photoacoustic imaging experiments show that the photoacoustic signal intensity and concentration of the contrast agent has a good linear relationship.After 4 h injection,the maximum value of the photoacoustic signal could be reached,and its intensity didn’t reduce within the range of 2 hours.Magnetic resonance imaging data shows that APPA-Fe3O4@PDI-PEG500-PMAA is a typical T2 magnetic resonance imaging contrast agent,the concentration of Fe and the relaxation rate(1/T2)has a good linear relationship,the transverse relaxation rate is 113.65 mM-1s-1.After irradiated by the laser of 730 nm for 4 min,the temperature of APPA-Fe3O4@PDI-PEG500-PMAA at the concentration of 1 mg/mL can be increased by nearly 27 ℃,which investigates a strong photo-thermal effect.(3)Design and synthesis a photoacoustic imaging contrast agent(c RGD-PDI NPs)which can target early thrombosis by using polypeptide cRGD.The photophysical properties and stability(photo,structure)were studied.The results show that the contrast agent has good water solubility(10 mg/mL)and a broad and strong absorption in the near infrared region of 600-750 nm.Almost no change of absorption intensity after irradiated by the laser of 635 nm shows that cRGD-PDI NPs has good light stability.The diameter remaining unchanged after 48 hours in serum suggests that the synthesized cRGD-PDI NPs retain excellent stability under biologically conditions.