Ph Sensitive Zinc Phthalocyanine Polymer Preparation And Performance Study

Cancer is a group of disease which can endanger human health, therefore, it has important significance in studying cancer treatment. So far, the main modalities of cancer treatment are surgery, chemotherapy, and radiotherapy. Sometimes surgery to remove tumors is ineffective because of cancer cell proliferation. Chemotherapy and radiation therapy can also damage normal tissue, while damaging cancer cells, and might even cause some serious complications. For comparison with the above, photodynamic therapy (PDT), which is a more efficient and minimally Invasive treatment, is increasingly being recognized as a promising new and attractive treatment modality for cancer. Photosensitizers play a crucial role in the photodynamic therapy (PDT) of cancer. The ideal photosensitizer should have a high photochemical quantum yield, high tumor uptake rate, strong absorption of red light, low dark toxicity and phototoxicity and so on. Comparing with the most used photosensitizers in clinical haematoporphyrin derivatives (HpD), Synthetic phthalocyanine (Pc), which have many attracted advantages such as easy modification, having good Photophysical and photochemical properties and low dark toxicity, is known as the potential drug for PDT investigations. Zinc phthalocyanine (ZnPc) prone to aggregation in aqueous solutions which lead to decrease its photoactivity. Therefore, a pH sensitive polymer poly(N,N-diethylaminoethyl methacrylate) (PDEA), which molecular chain can change during hydrophilic/hydrophobic transitions in aqueous solution, has been selected as a polymer carrier for ZnPc in this paper to obtain a new pH-sensitive polymer photosensitizer. In normal body fluid, the pH is about 7.4, the polymer photosensitizer chain collapse by pH-induced and encapsulated molecular ZnPc in it to decrease the photoactivity of ZnPc and reduce the toxic side effects on normal cell. While in tumor tissue, the pH is about 6.0, the polymer chain become swelling to expose ZnPc into the cytosol, the polymer photosensitizer exhibit high photoactivity on tumor damage under irradiation of visible light.In this dissertation, a pH-sensitive Zinc phthalocyanine random copolymer P(DEA-co-ZnMPc) was prepared by copolymerization of N,N-diethylaminoethyl methacrylate and zinc tetra(N-carbonylacrylic)aminophthalocyanine. The UV-vis spectroscopy indicated that P(DEA-co-ZnMPc) possessed a reversible pH response in aqueous solution, but poor water solubility. Therefore, atom transfer radical polymerization of zinc tetra(N-carbonylacrylic)amino -phthalocyanine and N,N-diethylaminoethyl methacrylate initiated by a poly(oxyethylene) glycol macroinitiator was synthesized. Despite its good water-solubility, the molecular chain structure of this block copolymer is difficult to control and identified. In order to get a pH sensitive polymer with clearly structure, a series of polyethylene glycol-b-poly(N,N-diethylaminoethyl methacrylate) block copolymers were synthesized by atom transfer radical copolymerization in the presence of PEG macroinitiator. Maleic anhydride, which was introduced as an acid end functional group, could covalently bond with ZnTAPc to abtain a pH sensitive polymer photosensitizer. Polymer structure was identified by 1H NMR, UV-vis, DLLS and AAS, and results indicated that every single chain was end-capped by a molecular ZnMPc.The new pH sensitive polymer photosensitizer presents a good reversible pH response in aqueous solution, and its critical pH values is about pH 7.4. Above the critical pH the copolymers aggregate to form micelles. The DEA block forms the micelle core while the hydrophilic PEG block extends into the solvent to form the micelle corona.In this work we used EPR spin-trapping technique to study the ability to generate singlet oxygen of the pH sensitive polymer photosensitizer (PEG110-b-PDEA611)-ZnTAPc under irridation with visible light in different pH solutions. The copolymers aggregate to form micelles and encapsulated ZnTAPc into the PDEA core in pH 7.4 solution, which limited the energy transfer between ZnTAPc and oxygen and inhibits 1O2 generation. While in pH 6.0 solution, the copolymer chain extends to expose ZnTAPc into the environment and product a amount of 1O2.The photoactivity of the the pH sensitive polymer photosensitizer on the oxidation of 1,3-diphenylisobenzofuran (DPBF), a singlet oxygen capture agent, was studied under irradiation (λ> 550 nm) with the visible light. And the DPBF could be oxidized quickly by the singlet oxygen, the results showed pH sensitive polymer photosensitizer prensents excellent photoactivity.A new pH sensitive polymer photosensitizer (PEG110-b-PDEAX)-ZnTAPc presents pH-introduced reversible micellar behavior in aqueous solution, could conrol its photoactivity in different pH conditions. It provides a new idea for cancer treatment and has an important theoretical significance.