Conjugation of Zn (II) phthalocyanine with polymeric brushes for improved photodiagnostics and photodynamic therapy of gastric tumours

The target-specific drug release which is depending on the pH of the medium appears precious approach for increasing of drug selectivity and further efficacy in photodynamic diagnosis (PDD) and therapy (PDT) of cancer. A strongly hydrophobic Zn (II) phthalocyanine (ZnPc) along with its liposomal formulates belongs to the clinically approved phthalocyanines for cancer photodiagnosis PDD and PDT. Nevertheless closed to the ideal photo-physicochemical properties the planar molecular structure of ZnPc easily forms aggregates which finally limit the phototoxic effect. Different strategies are on hand, all aiming to minimize the formation of photo-inactive associates. At present time, the polymeric carrier systems are still under development as carrier systems for biomedical applications. The present work evaluated the efficiency of two recently proposed graft - copolymers namely polyimide (PI)-graft-polymethacrylic acid (PAT2 and PAT3) as vehicles of hydrophobic ZnPc. The potential of the proposed polymeric brushes with great number of carboxylic groups, for conformational changes in different pH media, can be used for ZnPc release as studied by fluorescence spectroscopy. Complexes developed were investigated in vivo on rat model system of gastric carcinoma lesions for photodiagnosis and photodynamic treatment of neoplasia and compared with the application of ZnPcs solely. The contrast achieved of the fluorescence detection using polymer brushes - phthalocyanine conjugate is about twice higher that standard applied photosensitizer using same protocol and doses of application. The photodynamic treatment efficacy was also significantly improved allowing to receive full response using doses of 0,5-1 mg/kg of the conjugates. |To obtain same efficiency for the ZnPc PDT in the gastric lesions treated drug doses of 1,5-2 mg/kg had to be applied. Initially detected fluorescence signal and photo-bleaching dynamics were used for the monitoring of the processes of accumulation and photodynamic treatment processes.