Synthesis,Characterization And Activity Evaluation On Series Of Peptide-Phthalrcyanine Compounds

In recent years,photodynamic therapy(PDT)technology,as a noninvasive method of treating malignant tumors and age-related macular degeneration,which is different from the traditional cancer treatments,has drawn more and more attention of people.It has small side effects,good adaptability,the trauma of patients with small,but also with the traditional treatment of the advantages of co-treatment,in many of the cancer treatment has a wide range of applications.Photodynamic therapy is mainly through the injection of photosensitizer in vivo,and then through a certain wavelength of light irradiation,the photosensitizer to produce singlet oxygen,that can effectively kill the tumor tissue,and thus achieve the purpose of treatment of the tumor.Early photosensitizer drugs because of the maximum absorption wavelength is shorter,less targeted shortcomings,greatly limits the application of photosensitizer.Many people are beginning to work on new photosensitizers.Phthalocyanine has a conjugation system with 18? electrons,the maximum absorption wavelength is larger,and the phthalocyanine compounds are more stable,have strong singlet oxygen production ability,is one of the most promising photosensitizer candidatesThis topic synthsis of four targeting peptide conjugates zinc phthalocyanine with different length PEG chains by using phthalonitrile method,and they were covalently conjugated with three different polypeptide sequences(TLLRAK-Linker,TLLRAK-Linker-Glu and LLKATR-Linker).In the end,we obtained six zinc phthalocyanine compounds(Pc-1,Pc-2,Pc-3,Pc-4,Pc-5 and Pc-Control)that target EGFR receptors.By introducing PEG chain,the water solubility of phthalocyanine was solved.Then,the peptide sequence of TLLRAK,which specifically binds to EGFR receptor,was introduced by solid phase synthesis method,which solved the targeting problem of phthalocyanine.The six compounds(Pc-1,Pc-2,Pc-3,Pc-4,Pc-5 and Pc-Control)were characterized by high resolution mass spectrometry.The UV-Vis absorption spectra,fluorescence spectra and singlet oxygen yield of Pc-1,Pc-2,Pc-3,Pc-4 and Pc-5 were determined.The results show that the maximum absorption wavelength of the above five compounds(Pc-1,Pc-2,Pc-3,Pc-4,Pc-5)is near 680 nm,and it has good water solubility.The yield of singlet oxygen is between 0.49 and 0.60,and it has strong singlet oxygen production ability,which provides a prerequisite for future clinical studies.Through the bio-evaluation showed that the above five compounds(Pc-1,Pc-2,Pc-3,Pc-4 and Pc-5)have a strong phototoxicity,almost no dark toxicity.And Pc-Control phototoxicity is very weak,indicating that with the target peptide ligand does have a great impact on cell killing ability.In vitro imaging experiments showed that the five compounds(Pc-1 Pc-2,Pc-3,Pc-4 and Pc-5)could be specifically enriched in the mouse tumor,with strong targeting,and then using the two photosensitizers of Pc-3 and Pc-5 to carry out the mouse tumor model of the treatment experiment.We found that the tumor began to decrease after treatment,and eventually disappeared,the mouse weight did not change drastically,indicating that the two zinc phthalocyanine compounds are viable photodynamic therapy photosensitizer,the future of clinical trials with a certain guiding significance.