Research On Tumor Imaging And Treatment Based On Prussian Blue Nanoprobe

Cancer is one of the major diseases threatening human health.The development of stimulus-responsive nanomaterials can provide effective means for accurate diagnosis and effective treatment of cancer.Due to its good optical and magnetic properties,Prussian blue（PB）has been widely used in cancer imaging,targeted drug delivery and cancer treatment.However,the responsive imaging and treatment systems based on Prussian blue are rarely reported.Therefore,how to employ the characteristics of PB materials to design stimulus-response probes is an important means to improve the specificity of tumor imaging and treatment.The research content of this paper is divided into three parts:In chapter 2,based on the redox reaction characteristics of PB and ONOO^-,we constructed a responsive PB nanoprobe to detect ONOO^-by photoacoustic imaging and magnetic resonance imaging.After PB reacts with ONOO^-,Fe ^IIin PB is oxidized to Fe ^III,and the crystal structure of PB is destroyed,which causes changes in photoacoustic signals and magnetic resonance signals.Based on the above principles,we applied the PB probe to detect ONOO^-produced in drug-induced liver injury.The complementarity of photoacoustic and magnetic resonance dual-mode imaging can endow the probe with higher sensitivity,higher penetration depth and higher accuracy.This discovery opened up new ideas for PB to be used in the field of biosensor.In chapter 3,to overcome the interference factors caused by single photoacoustic signal output and to improve the imaging accuracy,we further designed and constructed a core-shell structure（Cu S@PB）nanoprobe,for ratiometric detection of ONOO^-.Among them,Cu S is relatively stable to ONOO^-as an internal standard,and the responsive PA signal of PB toward ONOO^-is used for ratiometric detection.The photoacoustic probe can be used for the imaging ONOO^-in the LPS-induced inflammation model.In chapter 4,to improve the specificity of tumor imaging and treatment,we constructed p H-responsive PB analogue nanoparticles（Gd Mn-PBA@F127）.Due to the doping of Gd and Mn ions,the new PB nanoparticles showed higher transverse relaxivity（r₂）,which is conducive to T₂-weighted magnetic resonance imaging;it also has p H-responsive photothermal therapy,photoacoustic imaging and magnetic resonance imaging capabilities.The nanoparticle has relatively stable photoacoustic signal,magnetic resonance signal,and photothermal performance in acidic conditions;while under neutral or alkaline conditions,its photoacoustic signal,magnetic resonance signal,and photothermal performance slowly decreased.Based on the above characteristics,the PB nanoparticles can exist stably in the acidic environment of tumors,and can be rapidly degraded in normal tissues to avoid long-term toxicity in vivo.This new PB nanoparticle can amplify the differences in imaging signal and photothermal effect between tumor and normal tissues,and improve the specificity of tumor imaging and treatment.Therefore,the novel PB nanoparticles have broad application prospects in the integration of tumor imaging and treatment in the future.