Design,Synthesis And Photothermal Application Of Azadipyrromethene-Based Near-Infrared Dyes

Cancer is a serious disease threatening human health in the 21st century.At present,the clinical cancer treatment is still mainly based on surgical treatment,radiotherapy and chemotherapy.However,the above-mentioned treatment methods are highly invasive,accompanied by strong toxic,side effects,and poor targeting ability.Therefore,the development of new tumor treatment methods is imminent.As a new treatment method for tumors,photothermal therapy?PTT?has been widely concerned because of its advantages with high efficiency,small trauma,fast recovery,etc.However,the current photothermal agents used widely in clinic are faced with many problems,such as low photothermal efficiency,poor photostability,poor biocompatibility,and the lack of theoretical guidance for constructing efficient phototherapy reagents,which seriously hinders the development of photothermal therapy.Therefore,the development of new near-infrared?NIR?photothermal materials with high stability and high photothermal conversion efficiency will effectively improve the treatment efficiency of tumors.In consideration of the advantages of aza-BODIPY dyes with strong NIR absorption,good stability,and easily modified chemical structure,they are chosen as the candidates.At last,a series of NIR aza-BODIPY-based photothermal reagents with excellent photothermal effect are designed and synthesized based on intramolecular photoinduced electron transfer and fluorescence resonance energy transfer mechanism.The main research contents of this paper are as follows.1.The design,synthesis and biological application of photothermal agent based on intramolecular photoinduced electron transfer and resonance energy transfer mechanismAccording to previous research work,intramolecular photoinduced electron transfer plays an important role in improving the photothermal conversion performance of molecules.First by,ba photothermal reagent A-1 is introducing dimethylamine group into the aza-BODIPY framework,which endowing A-1 intramolecular photoinduced electron transfer properties.Then another aza-BODIPY unit A-2 as a electron donor was synthesized and connected to A-1 through a click reaction to obtain PTT-A,which possess high energy utilization efficiency and high light-to-heat conversion performance under ultra-low power light irradiation owing to the resonance energy transfer from A-2 to A-1.By coating the PTT-A with polymer DSPE-m PEG₅₀₀₀,PTT-A nanoparticles?PTT-A NPs?were prepared with good water solubility and biological compatibility.It is proved by cell experiments that PTT-A NPs show low biotoxicity and an efficient photothermal treatment effect under ultra-low power light irradiation.2.The design,synthesis and photothermal properties exploration of pH responsive photothermal agentThe aza-BODIPY was selected as the dye precursor to synthesize the pH probe B₅,because of its maximum absorption wavelength and maximum emission wavelength locating in the NIR region.The phenolic hydroxyl group is used as a pH recognition site for quickly responding to changes of pH value.In alkaline environment,the protons on B₅ are taken away,which changed the intramolecular charge transfer effect?ICT?and resulted in weakened fluorescence.When the environment is acidified,protonation of B₅ leads to enhanced fluorescence.Based on this,B₅ can was used as a pH fluorescent probe for NIR imaging.The intramolecular ICT effect also has a greater influence on the intensity of the B₅ absorption spectra.The pH titration experiment shows the main absorption peak of B₅ gradually increases together with a certain degree of red shift under the condition of sequentially increasing alkalinity.In vitro experiments have shown that B₅ can achieve efficient photothermal effect under the excitation of a single near-infrared light source.