Synthesis,Characterization And Photosensitive Activity Of Silicon(?)phthalocyanines Substituted With Crgds As Anticancer Photosensitizers

Photodynamic therapy(PDT)is a rapidly developed new technology about tumor treatment in recent years.Photosensitizer is the key factor of therapeutic effect for PDT.Introducing two substituents in the axial site of silicon phthalocyanine(SiPcs)not only may adjust its physicochemical properties,but also could prevent the disadvantage of its inactivation due to ?-? aggregation of phthalocyanines.Thus,the research of axial substituted SiPcs as anticancer photosensitizers attracted researchers' attention.And,how to further improve the property of tumor targeting for SiPcs is a big challenge currently.Taking care about Cyclic peptides Arg-Gly-Asp peptide(cRGD)targets specifically to integrin ?v?3 which overexpressed on some types of cacer cells and tumor vascular endothelium surface cells,we synthesized and caracterized a series of SiPcs containing cRGD group in this paper.We have studied their physicochemical properties and photodynamic activities at same time,and the main results are summarized as follows.1.Firstly,SiPcs substituted with three kinds of oligomeric glycol have been synthesized.Secondly,the terminal hydroxy groups have been seletively azide to get six kinds of SiPcs.Finally,the above SiPcs have been conjugated with cRGD by click chemistry to obtain another six SiPcs.All of these compouds above have been characterized by MS,1HNMR,UV/VIS,and analyzed there purity by HPLC.According to document indexing,the above six kinds cRGD-modified SiPcs and six kinds azide-modified SiPcs have never been reported.2.Some physical and chemical properties for SiPcs have been studied,including molecule and florescence spectra,fluorescence quantum yield,photosensitivity and stabilities.The results show that:(1)The electronic absorption spectra of above compounds in DMF are typical for non-aggregated phthalocyanines with showing a Q-band at 673 nm.Their fluorescence quantum yields are between 0.34 and 0.51 with emission wavelenth at 680 nm,and their singlet oxygen quantum yields are between 0.29 and 0.37.They all have great light stability.(2)Compounds also exist as monomeric form in both water and 1%CEL solution with a Q band at 675 nm and 682 nm,respectively.All spectral characteristics abrove are conducive to PDT.3.In vitro cellular uptake and photodynamic anticancer activity of cRGD-modified SiPcs(7c,8c)and the terminal azide-modified SiPcs(5c,6c)has been studied yet.The results shows,(1)the uptake of 8c by human lung adenocarcinoma cells A549(integrin?v?3 over expression)is significantly higher than human breast cancer cells MCF-7(integrin ?v?3 not express),and the uptake of 8c by A549 cells could be inhibited competitively by cRGD.(2)In the presence of MCF-7 cells are more sensitive to SiPcs than A549 cells,the photodynamic killing activities of 7c against A549 cells and MCF-7 cells with a IC50 of 0.098 ?M and 0.110 ?M,respectively,and the photodynamic killing activities of 8c agaist A549 cells and MCF-7 cells with a IC50 of 0.026 ?M and 0.032?M,respectively.The results above suggests that cRGD-modified SiPcs(7c,8c)could target to integrin ?v?3 over expression cells A549.