Raft Of Ph Sensitive Prepared Zinc Phthalocyanine Block Polymers And Their Active Research

At present, cancer is a main reason for death. Therefore, cancer treatment research hasimportant significance. The traditional treatment methods include chemotherapy, radiotherapyand operative therapy, however, all these methods have their limitayions. Chemotherapy andradiotherapy will cause damaging effect on the normal physical tissue. For operative therapy, theinjury may be heavy and the effectiveness of therapy has not been satisfactory because of cancercell proliferation. The photodynamic therapy （PDT） is an efficient and minimally invasivetreatment route. This therapy includes three elements: photosensitizers, light and molecularoxygen. And photosensitizers play an important role in PDT. Synthetic phthalocyanine（Pc） isrecognized as a kind of high-quality photosensitizers because of its strong absorption in thevisible light region （600-800nm）, good light stability and low dark toxicity. In normal body fluid,the Ph is about7.4, however, the Ph is about6.0in tumor tissue. Based on the above, Zincphthalocyanine was supported on the pH-sensitive polymer in this paper in order to reach threepurposes: improve optical activity, increase selectivity for tumors and reduce phototoxicity.In this dissertation, the pH-sensitive monomer2-Diisopropylaminoethyl Methacrylate （DPA）and the hydrophilic monomer N-（2-Hydroxypropyl） Methacrylamide （HPMA） were synthesized.The pH-sensitive diblock copolymer PHPMA_n-b-PDPAmwere prepared via reversibleaddition-fragmentation chain transfer polymerization （RAFT）. The structure and properties ofPHPMA_n-b-PDPAmwere identified by1H NMR, FT-IR, GPC, UV-vis.The results showed thatthe diblock had low polydispersity （1.10<PDI <1.20） which was the typical characteristics ofcontrolled radical polymerization, and had good pH sensitivities in both aqueous solution andnormal saline. The diblock polymer were tested by DLS, FE-SEM and TEM. The resultsindicated that the diblock could form spherical micelles in both aqueous solution and normalsaline.The pH-sensitive polymer photosensitizer PHPMA_n-b-PDPAm-ZnTAPc were preparedsuccessfully by using ZnTAPc and PHPMA_n-b-PDPAmthrough amidation reaction. The UV-visspectroscopy showed that pH-sensitive polymer photosensitizer presented good pH sensitivitiesin both aqueous solution and normal saline，which attained the design purpose of pH-sensitivepolymer photosensitizer. The testing results of DLS, FE-SEM and TEM showed that the pH-sensitive polymer photosensitizer could form spherical micelles in aqueous solution, normalsaline and SBF solution and the partical diameters of micelles are in the range of100-200nm.The optical activity of PHPMA_n-b-PDPAm-ZnTAPc was studied by using the1,3-diphenylisobenzofuran （DPBF, a singlet oxygen capture agent） under irradiation with thevisible light （λ>550nm）, the results indicated that the pH-sensitive polymer photosensitizerpresent excellent photoactivity. In this work, the effects of illumination intensity, theconcentration of PHPMA_n-b-PDPAm-ZnTAPc and DPBF on oxidative degradation of DPBFwere also studied. The results showed that illumination intensity and concentration of DPBF hadgreat effect on oxidative degradation of DPBF, but concentration of PHPMA_n-b-PDPAm-ZnTAPchad little effect on it.electron paramagnanetic resonance （EPR） technique was used to study the ability ofgenerating singlet oxygen of PHPMA_n-b-PDPAm-ZnTAPc using2,2,6,6-tetramethylp （TEMP, asinglet oxygen capture agent） under irridation with visible light in pH6.0and pH7.4aqueoussolutions. The results showed that the pH-sensitive polymer photosensitizer had high ability togenerate singlet oxygen at pH6.0and had weak ability to generate singlet oxygen at pH7.4. ThepH-sensitive polymer photosensitizer aggregated to form micelles, and ZnTAPc wasencapsulated into micelles effectively in pH7.4solution, which greatly reduced the photoactivity.This results were consistent to the design purpose of the pH-sensitive polymer photosensitizer.The pH-sensitive polymer photosensitizer PHPMA_n-b-PDPAm-ZnTAPc presented excellentpH sensitivity and photoactivity. It had a high photoactivity in tumor tissues （pH6.0）, while hada low photoactivity in human normal tissues （pH7.4）. It provided a good theoretical basis forthe application of ZnTAPc in photodynamic therapy.