Engineering Cyclodextrin/Corannulene Inclusion Complex For Controlled Reactive Oxygen Species Production

Photodynamic therapy has getting more and more attention in the fight against diseases such as malignant tumor.As one of the basic elements of photodynamic therapy,the development of novel photosensitizer with high effiency and convenient preparation have been widely investigated.In recent years,fullerenes were found to possess remarkable photosensitive properties by many reseachers,thus expected to be applied to photodynamic therapy.As corannulene can be regarded as part of fullerene,it was selected to examine its ability for controlled reactive oxygen species?ROS?production.To address the poor water solubility of corannulene,a water-soluble gamma-cyclodextrin/corannulene??-CD/Cor?inclusion complex was prepared.The successful formation of?-CD/Cor complex was confirmed by ¹H NMR,UV-vis,IR and TGA.The purified complex maintained a molar ratio of 2:1??-CD:Cor?,as evidenced by the ¹H NMR,Job Plot and single crystal analyses of the?-CD/Cor complex.Gamma-cyclodextrin/perylene??-CD/Per?inclusion complex with the same inclusion ratio was selected as the control.Then we utilized ROS fluorescent probe to detect the capability of these two complexes aqueous systems in terms of ROS generation after the excitation of UV light??=365 nm?.It turns out that the curved Cor could generate ROS and controlling ROS production via regulating the Cor dose and duration of light irradiation.According to the test of ROS type,Cor could produce all three types of ROS,i.e.H₂O₂,HO·,and·O₂^-.To investigate whether dipole moment could be a universal parameter for ROS generation,we chose three other polycyclic aromatic hydrocarbons which also have dipole moments.After the ROS detection of four micellar solutions,we found it's the interplay of material's absorption spectrum and dipole that determines its behavior of ROS generation.Nevertheless,we demonstrated that Per without a dipole but with a UV absorption couldn't produce ROS,indicating dipole moment might be a robust factor to generate ROS.Photocytotoxicity and confocal fluorescence imaging tests were conducted into PC-3 cells with?-CD/Cor and?-CD/Per complexes.Upon?-CD/Cor treatment,the cell viability was shown to be noticeably linked to the time scale of irradiation,and the IC₅₀values of?-CD/Cor at a irradiation time of 15 min and 20 min were 39.6±2.6?M and8.8±4.5?M,respectively,whereas?-CD/Per complexes showed no photocytotoxicity under the same condition.Confocal fluorescence images of?-CD/Cor inclusion complex were taken before and after light irradiation and the results indicated that Cor can generate ROS upon light irradiation.In vitro blood hemolysis test and in vivo histological analysis proved the good biocompatibility of Cor.The current work demonstrated that?-CD/Cor inclusion complex was useful for improving the water solubility of Cor and it can generate ROS under the excitation of UV light,thus proving Cor is a novel photosensitizer for promising photodynamic therapy.