Study On The Preparation Of PH-sensitive Zinc Phthalocyanine Block Polymer By ATRP Method And Its Photoactivity

Nowadays, cancer has become the mankind's first killer. The conventional treatment methodsof cancer (i.e. surgical procedure, chemotherapy, and radiotherapy) all have been limited withsevere side-effects. Photodynamic therapy (PDT) is a promising and greater efficient approach withfewer side-effects for the treatment of cancer, which includes three components: photosensitizer,molecular oxygen and light. When activated by light of a particular wavelength and certain strength,the photosensitizer interacts with molecular oxygen (3O2) to produce singlet oxygen (1O2) with highoxidative activity. Then, the singlet oxygen (1O2) causes oxidative damage to cells, and eventuallyresults in cell death.Metallophthalocyanine (MPc) compounds have been proposed as second-generationphotosensitizers for PDT due to the strong absorption in the visible region (600~800nm) andextremely high singlet oxygen (1O2) generation ability. However, some problems are associatedwith existing MPcs, including poor selectivity for tumor cells and suboptimal photophysicalcharacteristics. In view of these properties, we attempt to design a series of pH-responsiveamphiphlic block polymer photosensitizers bonded zinc phthalocyanine (ZnPc) photosensitizer.This ZnPc photoactivity decreases dramatically at physiological pH (7.4) due to wrapping ZnPc intothe micelles, while these micelles cleave at endosomal pH (5.5~6.0) and ZnPc presents highphotoactivity due to its dispersivity. Therefore, in this paper, we prepared a series of novelpH-responsive polymeric photosensitizers by copolymerizing of methoxypolyethylene glycols(MPEG),2-(isopropylamino)ethylmethacrylate (DPA) and zinc tetra(methacryloyl moiety)aminopht-halocyanine (MeZnAPc). Polyethylene glycol (PEG) is a well-known to be highly hydrophilic andbiocompatible. PDPA homopolymer is a weak polybase, and its conjugated acid possesses a pKaof6.2. By addition of suitable polymer blocks improves accumulation and photodynamic activity ofZnPc.Firstly, a zinc tetraaminophthalocyanine derivative, zinc tetra(methacryloyl moiety)aminophth-Alocyanine (MeZnAPc)(with a double bond) and a halohydrocarbon polyethylene glycol macromolecular initiator (mPEG110-Br)(with Bromo-terminated functional group) wassuccessfully synthesized in order to obtain pH-responsive polymeric photosensitizers by atomtransfer radical polymerization (ATRP).Secondly, ATRP was employed as the polymerization technique to obtain a series of novelpH-responsive polymeric photosensitizers by copolymerizing of mPEG110-Br, DPA and MeZnAPc.In this paper, we have been designed two synthesis routes of one step and two steps preparationaccording to the preparation steps. One step preparation: A novel pH-responsive polymericphotosensitizers (PEG110-b-P(DPAn-co-MeZnAPcm)) were synthesized by copolymerizing ofmPEG110-Br, DPA and MeZnAPc. Two steps preparation: pH-responsive block copolymers(PEG110-b-PDPAn) were firstly prepared by copolymerizing of mPEG110-Br and DPA. Then, anothernovel pH-responsive polymeric photosensitizers ((PEG110-b-PDPAn)-MeZnAPcm) were synthesizedby copolymerizing of PEG110-b-PDPAnand MeZnAPc.These photosensitizers were characterized by1H NMR, FT-IR, UV-Vis spectroscopy, etc. Theresults indicated that the photosensitizers presented the well pH-responsive behavior around the pHrange6.0~6.5and the high photoactivity to1,3-diphenylisobenzofuran (DPBF). The result ofphotocatalysis oxidation of L-tryptophan (L-Try) suggested that zinc phthalocyanine could presenthigh photoactivity due to its dispersivity at pH5.5without formation of micelles, and itsphotoactivity decreased dramatically at pH7.4due to wrapping ZnTAPc into the micelles.Lastly, a comparison between PEG110-b-P(DPAn-co-MeZnAPcm) and (PEG110-b-PDPAn)-MeZn-APcmsuggested that (PEG110-b-PDPAn)-MeZnAPcmwere monomeric and non-aggregated speciesin water, and the content of MeZnAPc in these polymeric photosensitizers was three times thanthose determined by atomic absorption spectrometry. Therefore,(PEG110-b-PDPAn)-MeZnAPcmhave better application prospects in the field of photodynamic therapy.