PH-Responsive Fe(?)-Gallic-Acid Nanoparticles For In-Vivo Photoacoustic Imaging Guided Photothermal Therapy Visualization

Objective: Nanomaterials integrated with different therapeutic and diagnostic functional agents have attracted considerable attention due to their great potential in precision medicine.To date,large quantities of theranostic agents for simultaneous use in different imaging and therapeutic technologies,such as magnetic resonance imaging – photothermal therapy?MRI-PTT?,optical imaging – photodynamic therapy?PDT?,MRI-chemotherapy,computed tomography?CT?-PTT,and photoacoustic imaging?PAI?-PTT,were fabricated from individual functional agents,which could be detached from each other during circulation and metabolism in vivo,leading to different biodistributions and pharmacokinetics,inaccurate diagnosis,and poor therapy efficacy.Therefore,it is important to develop theranostic platforms based on single material which can serve as both imaging agent and therapeutic agent.Methods:?1?.The FeCl₃?10mM?solution and the Gallic Acid?15mM?solution were mixed with each other.The pH was adjusted to 3.7 with 0.1 M HEPES buffer solution and then incubated at room temperature for 2 h to obtain Fe???-Gallic Acid NPs,high resolution transmission electron microscopy?HRTEM?scanning,nano-laser particle size analyzer dynamic light scattering system?DLS?,UV-Vis spectrophotometer and other methods for characterization.The effect of Fe???-Gallic Acid NPs on in vitro photoacoustic and photothermal stabilization was evaluated by in vitro photoacoustic and photothermal cycles.The sensitivity and stability of the pH of the Fe???-Gallic Acid NPs solution were determined by the?0.1 M?HEPES buffer solution to varying pH and containing 10% FBS.?2?.MTT assay was used to investigate the cytotoxicity of Fe???-Gallic Acid NPs on 4T1 cells?mouse breast cancer cells?.After Fe???-Gallic Acid NPs exposured to near-infrared laser?808nm,0.5W / cm2,10min?,MTT experiment was used to investigate the effect of Fe???-Gallic Acid NPs effect of photothermal ablation of cancer cells.After 4T1 cells treated by medium containing Fe???-Gallic Acid NPs,a laser with a wavelength of 808 nm,the laser radiation of different power;the cells were subjected to Live-Dead staining to observe the survival status of cells after irradiation with different power laser cells.?3?The Fe???-Gallic Acid NPs solution was injected into the tumor-bearing mice through the tail vein.The mice was photographed by photoacoustic tomography?PAI?and treated with phototherapy.The tumor was recorded every day and the survival rate of mice were observed.The effect of Fe???-Gallic Acid NPs on the phototherapy of tumor in vivo was observed.after 45 days,tthe treatment group were killed and collected the main organs of mice for H & E staining,compared with the normal mouse organ tissue.Results: We have successfully synthesized a nanoparticle with a simple structure,high biocompatibility and high pH sensitivity.It is more reliable to adjust the size of Fe???-Gallic Acid NPs according to the pH value.It is more reversible to adjust the size of Fe???-Gallic Acid NPs according to the different pH value.Fe???-Gallic Acid NPs also exhibit good near-infrared absorption ability,excellent photothermal conversion efficiency and photodynamic properties,which make it have perfectly imaging effect in photoacoustic imaging.Intravenous injection of Fe-Gallic Acid NPs to tumor-bearing mice in vivo,combined with photoacoustic imaging and photothermal therapy can be accurate and complete elimination of tumor cells.In this paper,pH-responsive nanoparticles were constructed.The study of photochromic imaging and photothermal therapy in animal models provided a new strategy for the development of cancer diagnosis and therapeutic agents.Conclusion: a new type of PAI-PTT nanotheranostic agent based on pH-sensitive Fe???-gallic-acid complex was successfully developed.The complex has a strong NIR absorbance and can reversibly aggregate into nanoparticles with a size that is controllable by simply changing the solution pH value.the Fe???-gallic-acid nanoparticles present low toxicity and excellent photothermal ablation of cancer cells,so that they can serve as an efficient photothermal agent.Fe???-gallic-acid nanoparticles are a highly effectively photothermal agent for NIR light-induced tumor ablation.In addition,no acute toxicity was observed for the Fe???-gallic-acid nanoparticles in our experiments,demonstrating their excellent biocompatibility.