Synthesis And Photothermal Photodynamic Properties Of Perylene Imide-sugar Compounds

Cancer has become one of the most serious diseases affecting global health.The incidence of malignant tumors was approximately 3.929 million,and the number of deaths was as high as 2.338 million in China in 2015.In the past ten years,the incidence of malignant tumors has increased by 3.9%per year,and the mortality rate has increased by2.5%each year,which seriously threatens people's health.Traditional tumor therapy will bring many serious side effects to patients,and the treatment effect is often not ideal.In recent years,new phototherapy methods of photothermal therapy and photodynamic therapy has received widespread attention in cancer treatment due to its advantages of low toxicity and high selectivity.The mechanism of PDT is that the photosensitizers?PSs?are activated to generate reactive oxygen species?ROS?after the pecific wavelength light irradiate,which kills tumor cells through apoptosis and necrosis.PTT uses photothermal agents?PTA?to absorb near-infrared light and convert it into heat,which causes tumor cell death.Due to the inherent thermal resistance effect of PTT and the local hypoxia and limited light penetration depth inherent of PDT tumors,the effect of its cancer treatment is affected.Therefore,we designed and synthesized a mannose-modified perylene monoimide derivative,which has good photothermal effect and photodynamic effect,and can be used for near-infrared fluorescence and photoacoustic imaging dual-mode guided photothermal and photodynamic combined treatment of cancer.It provides new development prospect for the perylene monoimide derivative multi-modal imaging to guide the photothermal and photodynamic synergistic treatment of cancer.Perylene monoimide?PMI?is a class of fused ring conjugated compounds with excellent chemical,photothermal stability and good optical properties.PMI has poor water solubility due to strong?-?aggregation,which limits its application in biological experiments.Carbohydrates are an important class of biomolecules with good water solubility and biocompatibility.Herein,the mannose-modified perylene monoimide compound PMI-3Man and the dendritic lactose-modified QDI compound QDI-6Lac were designed and synthesized.The structure was characterized by ¹H NMR,¹³C NMR and HRMS.The assembly behavior of PMI-3Man was studied by UV-vis,fluorescence and circular dichroism spectroscopies.And its assembly morphology was observed by scanning electron microscope?SEM?.The compound PMI-3Man has strong absorption in the 600-800 nm region and exists as an aggregate in an aqueous solution.According to the photodynamic performance study,the DPBF and PMI-3Man mixed solution was irradiated with 690 nm laser for 120 min,and the characteristic peak of DPBF at 415 nm gradually decreased by41.6%.Indicating that the compound PMI-3Man has good light stability and excellent photodynamic effect.The photodynamic therapy effect of the compound PMI-3Man was studied by light-MTT experiments.The results showed that the compound PMI-3Man showed obvious toxicity to Hela cells and MCF-7 cells under visible light irradiation,and showed excellent photodynamic activity.Confocal imaging experiments show that the compound PMI-3Man is localized to the lysosome.Through near-infrared mouse imaging experiments,the compound PMI-3Man was injected into the 4T1 tumor-bearing mice by tail vein,and the fluorescence at the tumor site reached the strongest at about 11 h,indicating that it can target tumor cells.Therefore,the mannose-modified compound PMI-3Man has potential application value in cancer treatment.