Synthesis, Targeting Modification And Activity Evaluation Of Water-soluble Zinc Phthalocyanines

Photodynamic therapy is emerged in the 1980s, a new method of treating tumours, developed in recent years. It is based on photodynamic effect. First, the photosensitizer (PS) is injected into the body. After a period of systemic PS distribution it selectively accumulates in the tumor.Then, Irradiation activates the PS and in the presence of molecular oxygen triggers a photochemical reaction that culminates in the production of singlet oxygen (1O2). Generating cell toxicity leads to cell damage and death.Phthalocyanine compound, as a member of the second generation of photosensitizers, has strong ability of singlet oxygen generation, is extremely potential. In order to further improving the selectivity in the tumor sites, the third generation of photosensitizers is based on the second generation by coupling with some special chemicals. PSs are covalently attached to various molecules that have some affinity for neoplasia or to receptors expressed on specific tumors.Highly expression of folate receptor on the surface of tumor cells, and the expression is highly conservative in normal tissues. Based on the expression differences, can realize the active targeting transport for specific binding between folic acid-photosensitizer conjugates and folate receptor on the surface of tumor cells.Then, studying on the treatment of tumors.This topic starting with solving the water-soluble of zinc phthalocyanine photosensitizers, synthesized two kinds of symmetric zinc phthalocyanine (PcZn1 and PcZn2) through increasing its water solubility modified by polyethylene glycol and glycerol on phthalocyanine. Then, synthesized two kinds of water-soluble asymmetric zinc phthalocyanine (PcZn1-lys and PcZn2-lys) through the method of solid phase synthesis to solve the difficult problem of purification.Last, we got a kind of folic acid-photosensitizer (PcZn1-lys-FA) conjugate through targeted modification of PcZn1-lys with folate acid.Identifying structures of the five species of phthalocyanine compounds by’HNMR and ESI-MS. Then, the spectral properties, quantum yield, fluorescence lifetime and singlet oxygen quantum yield of PcZn1, PcZn1-lys and PcZn1-lys-FA were determined. Finally, biological activity evaluation of PcZnl-lys-FA carried out by experiments in vivo and in vitro.The maximum absorption wavelength of the three kind of polyethylene glycol modified zinc phthalocyanine at 682 nm,10 nm redshift than commercially available PcZn. Quantum yield and the singlet oxygen quantum yields are around 0.13 and 0.50, decreased comparing to 0.18 and 0.67 of PcZn, but did not produce substantial effect. Finally, through the cell experiment and animal vivo imaging, verified the high specific binding ability of the folic acid ligand and tumor cell surface folic acid receptors.