| The high incidence and mortality of cancer pose a serious threat to human health.The current clinical treatment of cancer mainly includes surgical resection,chemotherapy and radiotherapy.Although these three methods can remove or inhibit tumor growth to a certain extent,they also have hidden dangers of causing tumor metastasis and toxic side effects.In addition,continuous administration of chemotherapy and radiotherapy can also lead to increased drug resistance of tumor cells,which leads to a gradual decline in efficacy.Therefore,it is still a challenging international research topic to develop new controllable cancer therapies with high efficiency and low toxic side effects.Photothermal therapy is an emerging cancer therapy method that uses active or passive targeting means to aggregate photothermal reagents with photothermal transformation ability at the tumor site,and converts the light energy absorbed by them into heat energy through near-infrared light irradiation in vitro,thereby raising the temperature at the tumor site and activating the apoptosis pathway of tumor cells.Photothermal therapy has attracted wide attention because of its spatiotemporal control of tumor therapy.At present,the strategies to improve the efficacy of photothermal therapy mainly focus on improving the photothermal conversion efficiency of photothermal reagents.Considering that photothermal therapy is a strategy of apoptosis pathway triggered by high temperature generated by photothermal transformation,if tumor cell penetration efficiency of photothermal materials can be selectively regulated to accurately locate photothermal reagents and achieve intracellular photothermal transformation to the maximum extent,the effect of photothermal therapy will undoubtedly be improved.The essence of regulating the photothermal reagent cell penetration efficiency is to regulate the surface interface interaction between photothermal reagent and cell membrane.Although previous studies have shown that size,hydrophobicity and charge can affect the degree of interaction between nanomaterials and cell membranes,considering the chirality characteristics of phospholipid bilayer and integrated membrane proteins,the study of the chirality of nanomaterials on the regulation of cell penetration efficiency is undoubtedly helpful to reveal the mechanism of interaction between living bodies at the molecular level.Based on the above research background,this paper firstly constructs chiral supramolecular nanoparticles by the host-guest interaction between arginine(Arg)and watersoluble pillar[5]arene(WP5).First by ultraviolet titration experiment proves that the combination of WP5 and Arg ratio of 1:1,moreover through nuclear magnetic titration experiment according to the changes of the chemical shift to calculate the binding constant of WP5?D/L-Arg Ka=(1.017±0.254)×103 M-1、Ka=(1.024±0.259)×103 M-1.By transmission electron microscopy(TEM)and melvin particle size instrument found WP5?D/L-Arg formed in aqueous solution,the core-shell structure of about 450 nm.Secondly,the chiral characteristics of the supramolecular assemblage were confirmed by circular dichroism spectra.On this basis,the liposome was used to simulate the cell membrane,and through the isothermal heat drops of quantitative method and fluorescent confocal microscope photographs reveal chiral assembly body and the differences of the liposome and cells,found that compared with the WP5?L-Arg,WP5?D-Arg and liposomes and the cell has a stronger interaction.In addition,the anticancer drug doxorubicin hydrochloride(DOX)and the photothermal agent indocyanine green(ICG)were simultaneously loaded into the chiral supramolecular assembly to further endow the chiral supramolecular assembly with the combination of drug and photothermal tumor therapy.The final results show that compared with WP5?L-Arg+DOX+ICG,WP5?D-Arg+DOX+ICG has better effect of cancer therapy,showed that chiral important strategy can be used as therapeutic effect of field control.At the same time,arginine grafted aniline tetramer(ArgTANI)was constructed.By TEM observation,it was found that ArgTANI could self-assemble into spherical nanoparticles with the size of about 50 nm in water.In addition,by studying the UV-Visible-near-infrared absorption spectra of ArgTANI assemblages with different chirality under different pH conditions,it is found that they have great application potential in the photothermal treatment of tumor in the NIR-Ⅱ biological window.Fluorescence confocal microscopy was used to observe the localization of ArgTANI self-assembly with different chirality in tumor cells.The results showed that ArgTANI self-assembly with different chirality could successfully enter into tumor cells.Then CT26 cells were selected to carry out CCK-8 detection on ArgTANI with different chirality,which proved that the material had certain killing effect on colon cancer cells and different chirality materials had different killing effect on tumor cells.It was again proved that the chirality of the material had an effect on cell penetration efficiency and the difference would be further increased under laser irradiation.Finally,the antitumor mechanism of the self-assembled ArgTANI with different chirality was investigated.The antitumor activity of different chiral ArgTANI was mediated by mitochondrial apoptosis pathway through the reduction of mitochondrial membrane potential.Based on the ideal photothermal properties and biocompatibility of ArgTANI,we continue to introduce chiral functions into ArgTANI/pillar[5]arene supramolecular assemblies with high photothermal conversion efficiency and pH stimulation responsiveness.The regulation rule of photothermal reagents of chiral supramolecular assembly on cell penetration efficiency was revealed through circular chromatograph,ITC,fluorescence confocal,in vitro and in vivo biological experiments,and finally the photothermal conversion efficiency was improved and the photothermal reagents were accurately located at the tumor site,providing a unique solution for the hot issue of tumor photothermal treatment. |
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