Synthesis And Bioimaging Application Of Multifunctional Perylene Diimide Nanoparticles

Bioimaging technologies combine the advantages of material technology and modern biology,which can obtain the information of organism structure and function.It has the advantages of high efficiency,sensitivity and non-destructive.Among them,optical imaging technology makes full use of the permeability and operability of light,and develops rapidly in the field of agriculture and oncology medicine.With the complexity and deepening of biological research,traditional imaging agents have been difficult to meet the growing research needs of biology.Nanoparticles used in imaging not only need to provide high-quality imaging,but also have the characteristics of stimulation response to adapt to more use scenarios.Furthermore,these smart nanoparticles can not only "find problems" through imaging,but also play a therapeutic role to achieve "solving problems" as "functionality".This can be achieved by adjusting the properties of nanoparticles.As a new generation of contrast agent,nanoparticles are gradually emerging in bioimaging.Based on the strong modification ability of nanomaterials,their properties can be controlled by physical or chemical method,so as to make up for the defects of traditional contrast agents and realize intelligent imaging.Perylene diimide(PDI)is a kind of fluorescent dye with excellent optical properties,which is widely used in the fields of photoelectricity and coating.As an organic dye,the absorption and emission of PDI are in visible to near infrared region,and its optical properties can be controlled by molecular modification,considered as an ideal imaging agent.At present,PDI nanoparticles have been reported in the field of agricultural and cancer treatment.However,owing to the strong ?-? stack,PDI has low water solubility and high toxicity.In addition,the synthesis and modification process of PDI are relatively complicated,which will limit its further application.Currently,single mode fluorescence imaging of PDI is not satisfied with the growing demand,and improving its functionality is the current trend.Based on the above background,this article takes PDI as the research object,starting from the charge,size and optical performance regulation,through different modification methods to improve the water solubility and functionality of PDI.We prepared functional and responsive nanoparticles,and finally realized the imaging application of pest management,tumor imaging and cancer theranostics.The results of this article are mainly divided into three chapters:1.The charge modification of PDI,to improve water solubility and fluorescence imaging effect,and further realize the efficient gene pest control after vector tracing.In this chapter,a kind of star like cationic polymer SPc was synthesized.PDI dye(PDI-40H)was coated by self-assembly method to prepare water-soluble nano particles SPc/PDI with positive charge,to improve the water-soluble and cell uptake effect of PDI.Firstly,SPc was synthesized by ATRP with pentaerythritol and DMAEMA as basic materials.By improving the purification method,SPc is not only easy to be prepared,but also has low cost.Secondly,SPc/PDI with positive charge greatly improves the water solubility and cell uptake efficiency of PDI,which can trace the location of SPc in cells by fluorescence imaging.Finally,according to the imaging information,SPc can stably combine dsRNA,enhance the cell uptake effect and stability of dsRNA,inhibit the growth of pests by feeding and injection,and achieve the goal of efficient gene insecticidal.This work plays an important role in green agriculture2.The assembly modification of PDI,to increase the characteristics of pH response,and realize intelligent tumor imaging.In this chapter,a linear amino acid polymer(PNL)with PDI as terminal group and polyisoleucine as chain was synthesized PNL has good water solubility and can be assembled into spherical nanoparticles in water.The outer shell of PNL is composed of polyisoleucine with high biocompatibility,which reduces the accumulation of PDI with high biosafety.It is important that in a low pH microenvironment(lysosome and tumor tissue),the increased force between PNL segments produces a strong aggregation,reflecting the regulation of pH-responsive assembly.After injection,PNL circulates and penetrates in a smaller size,and the effect of aggregation will be improved at the acidic tumor site.Combined with the NIR optical properties,PNL can achieve tumor imaging from the way of fluorescence and photoacoustic,clearly show the location and depth of tumor,and provide a powerful tool for tumor therapy3.The optical properties modification of PDI,to improve the photothermal effect and pH response fluorescence of PDI in NIR region,and to achieve effective imaging-guided PTT in vitro/vivo.Firstly,piperazine was modified to two bay positions of PDI,and water-soluble PEG was added by esterification.It forms the amphiphilic macromolecule with PDI as core and PEG as shell.This macromolecule can be assembled into 65 nm particles(PPDI-NPs)in water.Due to the electronic effect,PPDI-NPs has strong absorption and high photothermal conversion efficiency at 670 nm(43.5%).In the weak acidic microenvironment,the PET effect of PPDI-NPs will be blocked due to the N-protonation of piperazine,resulting in 760 nm NIR emission.PPDI-NPs can rich in the tumor site to achieve NIRF/PA/IRT imaging,not only can clearly show the location and boundary of tumor,but also provide time window information for PTT.Exposed to a 660 laser(0.5W/cm2),PPDI-NPs can heat up rapidly and burn tumor tissue effectively.In addition,owing to the good biocompatibility and water solubility of PEG,PPDI-NPs showed low toxicity in vitro/vivo.This work provides a new organic reagent for the cancer PTT.