Study On Synthesis And Properties Of Small-Molecular Targeted Anticancer Photosensitizer Based On Silicon(Ⅳ) Phthalocyanine

Since 1980,the application of phthalocyanine compounds in Photodynamic Therapy(PDT)has attracted considerable attention,phthalocyanine have many advantages,such as stable structure,appropriate absorption spectrum.Therefore,it was considered to be one of the most promising second-generation photosensitizer,but it still has the deficiency of poor uptake and targeting.Molecular target-based anticancer drugs can specifically recognize and kill tumor cells,and then become the main categories of anticancer drugs.In this paper,based on our experience on photosensitizer for many years,the active structure domain of small molecular target-based anticancer drugs and phthalocyanine was coupled by polyethylene glycol linker chain to obtain the conjugate,two series of small molecule targeted anticancer photosensitizer,based on silicon(IV)phthalocyanine have been synthesized.Then,the photophysical and photochemical properties and photodynamic activity in vitro were investigated,and to explore them structure-activity relationship.The main work and results are summarized as follows:1.The appropriate of linking site on gefitinib and erlotinib was coupled to silicon phthalocyanine by polyethylene glycol linker chain to obtain five small molecular target-based anticancer drugs-silicon(Ⅳ)phthalocyanine conjugates which no report.And their structure were characterized by High-Resolution Mass spectrometry(HRMS)and Nuclear Magnetic Resonance spectroscopy(1H NMR).For comparative study,a tri(ethyl glycol)-monomethylether-phthaIocyanine was obtained as a control.2.The photophysical and photochemical properties of the maximum absorption wavelength(λmaxabs),the maximum excitation wavelength(λmaxex),fluorescence quantum yield(φF)and singlet oxygen quantum(φ△)were measured by the UV-Vis spectra,the fluorescence emission spectrum and the ability of photosensitization generate of singlet oxygen of these five small molecular target-based anticancer drugs-silicon(Ⅳ)phthalocyanine conjugates in DMF solvent,cell culture media and in different solvents.The result show that these conjugates were almost form of monomer in DMF cell culture media.Most of conjugates were form of monomer in cell culture media and different solvents.The gefitinib or erlotinib had no significant effect on λmaxabs and λmaxex of the phthalocyanine,but had a certain effect on φFandφ△,because of the degree of the polyethylene glycol chain length also had a certain effect on φF and φ△ of theses conjugates.3.The cytotoxicity and photodynamic activity of these conjugates,including the cellular uptake,reactive oxygen species generation ability,subcellular localization and cytotoxicity were investigated.The results show that all of these conjugates exhibit high cytotoxicity upon irradiation and good specificity on HepG2 cells.The cellular uptake,reactive oxygen species generation ability and photocytotoxicity on HepG2 cell were correlated with the length of polyethylene glycol chain.Four phthalocyanine conjugates were mainly located in the lysosome of HepG2 cells.