Synthesis And Thermo-Sensitive Effect Of Perylene Monimide And Cyclodextrin Derivatives

As one of the major diseases,cancer is a serious threat to global health.With the continuous development and progress of society,the incidence of cancer has increased sharply.Currently there are many treatment strategies for cancer,such as chemotherapy,radiation and surgery.At the same time,photothermal therapy has gained widespread attention due to its advantages in cancer treatment,such as controllable treatment process and enhanced tumor eradication efficiency.However,it is difficult to completely eradicate large tumors using traditional photothermal therapy because of the residual tumor mass at the treatment edge.Transcatheter arterial embolization（TAE）has become a first-line treatment for unresectable or hypervascular tumors.It is the gold standard for unresectable liver cancer because of its quick response and easy combination with other therapies.However,there are many defects in clinical practice of TAE.Many embolization materials have several dangerous drawbacks in clinical use,such as catheter adhesion,incomplete and untargeted embolization,recanalization,and uncontrollable presence in vivo.In this paper,we designed a series of cyclodextrin modified perylene monoimide derivatives,which had good thermo-sensitive and photothermal effects,and could precipitate solid to cause vascular embolization,which could be used in the dual mode of photothermal therapy and vascular embolization for cancer treatment.This design provides a new prospect for the development of perylene monoimide multimodal guided photothermal therapy for cancer.Perylene monoimide（PMI）is a kind of thick cyclic conjugated compound with excellent assembly ability,high quantum yield,high photothermal stability and good optical properties.The strongπ-πaggregation of PMI itself leads to its poor water solubility,which limits its wide application in biological experiments.Cyclodextrins are a class of important macrocyclic biomolecules with good water solubility and biocompatibility,and have the ability to encapsulate guest molecules in aqueous solution.Based on this,a series of cyclodextrin-modified perylene monoimides（PMI-P-2CD,PMI-PR-2CD,PMI-PS-2CD）were designed and synthesized in this paper.The structures of the compounds were characterized by ¹H NMR,¹³C NMR and HRMS.The assembly behavior of compounds PMI-P-2CD,PMI-PR-2CD and PMI-PS-2CD was characterized by UV-Vis,fluorescence and circular dichroism spectra,and their particle sizes were observed by dynamic light scattering（DLS）.The compounds all have strong absorption in the region of 550-750 nm and exist in the form of assembly in aqueous solution.The temperature-sensitive properties showed that the compound had good temperature-sensitive properties.When the temperature rose,the solution precipitated out of the solid and became turbid.The results of photothermal properties show that the compounds have good photothermal properties and stability.All the compounds are good photothermal materials.The cytotoxicity of compounds PMI-P-2CD,PMI-PR-2CD and PMI-PS-2CD was studied by MTT assay and staining assay of living dead cells.The results showed that none of the compounds had obvious toxic and side effects on HepG2 cells,but had obvious toxic and side effects under light.The results showed that all the compounds had good biocompatibility.Fluorescence confocal imaging experiments showed that all the compounds could enter the cells,which provided the basis for photothermal therapy in mice.HepG2 tumor-bearing mice were treated with the compound PMI-PR-2CD through tail vein for about 20 min through the selection of photothermal therapy time in vivo and near-infrared mouse imaging experiments.Therefore,these compounds modified by cyclodextrin have potential application value in the treatment of cancer.