Self-assembled Nanoparticles With BODIPY And PC-RGD

Recent years,more and more attentions have been paid to the diagnosis and treatment of malignant tumors.Accurate detection and effective elimination of tumor cells in vivo has become the main research goal in this field.Fluoroboron fluorescent dyes（BODIPY）are widely used in cancer diagnosis due to its easy modification and high fluorescence quantum yield.In addition,its unique optical characteristics make it possible to effectively eliminate tumor cells through phototherapy while diagnosing tumors.At present,the wavelength of most of BODIPY molecules can’t reach the near infrared region,and lack sufficient water solubility and biocompatibility,so it is difficult to be applied in organisms.In order to solve these problems above,six new BODIPY molecules were designed and synthesized in this paper.By self-assembly with DSPE-PEG₂₀₀₀-MAL-RGD（PC-RGD）,six nanoparticles were formed to improve their water solubility,biocompatibility and targeting,and their photodynamic and photothermodynamic properties were evaluated,respectively.（1）The core skeleton of fluoroboron dipyrrole compounds was synthesized from 2,4-dimethylpyrrole.Three modified small molecular materials were introduced into BODIPY at 3,5 sites by Knoevenagel condensation reaction.Six novel BODIPY molecular structures were obtained,whose maximum fluorescence wavelength was 750,850,685,775,650 and 775 nm,respectively.（2）The long chain of（DSPE-PC-MAL）with phospholipids and maleimide wasconnected to the target group RGD with thiol group to form an amphiphilic compound（PC-RGD）.PC-RGD and BODIPY form nanoparticles by self-assembly to improve targeting as well as water solubility and biocompatibility of BODIPY.The properties of BODIPY were tested by fluorescence,ultraviolet,SEM and TEM,and the results showed that BODIPYs were successfully coated by PC-RGD.After self-assembly,the nanoparticles were about 100 nm in size and uniform in morphology.Cytotoxicity experiments showed that the prepared materials had low toxicity in the experimental concentration range;flow-cytometry experiments and confocal solid-state experiments showed that BODIPYs were successfully coated.Experiments showed that the target group RGD could significantly enhance the active targeting of materials.（3）The photodynamic and photothermal therapeutic capacity of six BODIPY-PC-RGDs were measured,and the efficiencies were about 43%and 25%.Results were proved by experiments that iodine is the main factor to improve the efficiency of phototherapy.Six new BODIPY nanoparticles have been designed and synthesized.The effect of conjugation degree on molecular optical properties has been proved by experiments.The introduction of iodine is the main reason for improving photodynamic and photothermal efficiency.This provides a new idea for the integration of BODIPY and its derivatives in cancer diagnosis and treatment.