E. Borisova, Ts. Genova, A. Gisbrecht
Institute of Electronics, Bulgarian Academy of Sciences, 72, Tsarigradsko Chausse, Blvd., 1784 Sofia, Bulgaria.
Institute of Macromolecular Compounds, Russian Academy of Sciences, Bolshoi pr. 31, St. Peterburg, 199004, Russia
V. Mantareva, I. Angelov
Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Acad. G. Bonchev, str., Bld. 9, 1113 Sofia, Bulgaria
Al. Khorovodov, I. Agramovich, M. Klimova, O. Semyachkina –Glushkovskaya
Saratov State University, 83 Astrakhanskaya Str., Saratov, 410012, Russia
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 photodiagnosis and photodynamic therapy (PDT) of cancer. A strongly hydrophobic Zn (II) phthalocyanine (ZnPc) along with its liposomal formulates belongs to the clinically approved phthalocyanines for cancer 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 minimise the formation of photo-inactive associates. At present 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. Light doses used in both types of treatment were 200 J/cm^2 on 670 nm irradiation. Initially detected fluorescence signal and photo-bleaching dynamics were used for the monitoring of the processes of accumulation and photodynamic treatment processes.
Acknowledgments: The investigations related to development of conjugates between polymer brushes and phthalocyanines were supported by the National Science Fund of Bulgarian Ministry of Education and Science under grant #KP06-N29/11/18.12.2018. The investigations related to in vivo investigations of PD and PDT efficiency on gastric cancer were supported by Russian Science Foundation project #18-15-00139.
Dr. Ekaterina Georgieva Borisova
Institute of Electronics, Bulgarian Academy of Sciences, Associate Professor
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