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DOI: 10.15507/0236-2910.027.201701.093-107
TARGETED DELIVERY OF DOXORUBICIN BY EXOGENOUS BIOCOMPATIBLE NANOVEKTORS IN EXPERIMENTAL NEOPLASIA
Andrey V. Zaborovskiy
Associated Professor of Chair of Pharmacology, Yevdokimov Moscow State University of Medicine and Dentistry (20 bd. 1 Delegatskaya St., Moscow 127473, Russia), Ph.D. (Medicine), ORCID: http://orcid.org/0000-0002-7923-9916, This email address is being protected from spambots. You need JavaScript enabled to view it.
Aleksandr V. Kokorev
Head of Chair of Physiology, Medical Faculty, Obninsk Branch of National Research Nuclear University (1 Studgorodok, Obninsk 249030, Russia), Ph.D. (Medicine), ORCID: http://orcid.org/0000-0003-3316-1639, This email address is being protected from spambots. You need JavaScript enabled to view it.
Yekaterina P. Brodovskaya
Postgraduate Student, Chair of Anesthesiology and Rheumatology, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), ORCID: http://orcid.org/0000-0002-1060-9843, This email address is being protected from spambots. You need JavaScript enabled to view it.
Sergey A. Firstov
Postgraduate Student, Chair of Anesthesiology and Rheumatology, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), ORCID: http://orcid.org/0000-0003-1961-7708, This email address is being protected from spambots. You need JavaScript enabled to view it.
Olga V. Minayeva
Associated Professor of Chair of Anesthesiology and Rheumatology, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), Ph.D. (Medicine), ORCID: http://orcid.org/0000-0002-6154-3434, This email address is being protected from spambots. You need JavaScript enabled to view it.
Oleg A. Kulikov
Associated Professor of Chair of Pharmacology and Clinical Pharmacology with a course of Pharmaceutical Technology, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), Ph.D. (Medicine), ORCID: http://orcid.org/0000-0003-4411-677X , This email address is being protected from spambots. You need JavaScript enabled to view it.
Natalya N. Chervyakova
Associated Professor of Chair of Anesthesiology and Rheumatology, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), Ph.D. (Medicine), ORCID: http://orcid.org/0000-0002-7904-3948, This email address is being protected from spambots. You need JavaScript enabled to view it.
Vyacheslav Yu. Medvezhonkov
Postgraduate Student, Chair of Normal and Pathological Anatomy, National Research Mordovia State University (68 Bolshevistskaya St., Saransk 430005, Russia), ORCID: http://orcid.org/0000-0002-4373-6566, This email address is being protected from spambots. You need JavaScript enabled to view it.
Introduction: The article presents the method of obtaining the conjugate of the anticancer chemotherapeutic agent doxorubicin with the exogenous double-stranded DNA of the sturgeons is proposed (the source: commercial drug “Derinat”). The optimal conditions for synthesis of conjugate (pH, temperature and the mass ratio of the components), ensuring the highest degree of binding the chemotherapeutic agent to a carrier, were picked out. The investigation of the toxicity and specific antineoplastic activity of the synthesized complex was conducted.
Materials and Methods: The synthesis of DNA-doxorubicin conjugates was performed by mixing of the aqueous DNA solution, phosphate buffer and aqueous doxorubicin solution. The mixture was incubated for 60 minutes at constant temperature and continuous shaking. Clearing of the conjugate from the non-encapsulated chemotherapeutic agent was made by ultrafiltration method. The performance of the drug toxicity was established on the intact mice in compliance with the accepted standards. The antineoplastic activity was evaluated upon the Tumor Growth Inhibition Index and Metastasis Inhibition Index in mice with the transplanted lung Lewis carcinoma (LLC). Specific anti-tumor activity was studied in the toxically equivalent doses of the drug.
Results: It is found that administered in the toxically equivalent doses conjugate has a higher antitumor activity than soluble drug (up to 35 % by volume of the tumor and 51 % by the index of tumor growth inhibition). It is found that all investigated forms except the water soluble doxorubicin 0,5 LD10, significantly reduced the number of tumor metastases in the lungs. The number of metastases in animals treated with DNA-conjugated drug was lower than in the animals that were treated with aqueous doxorubicin, but these differences were not statistically significant.
Discussion and Conclusions: The most probable mechanism of increasing antitumor activity of the DNA-conjugated doxorubicin is a selective accumulation of the drug in the tumor tissue, due to the endocytosis of the DNA complex.
Keywords: doxorubicin, anticancer drug, targeted drug delivery, DNA conjugate, toxicity
For citation: Zaborovskiy AV, Kokorev AV, BrodovskayaYeP, Firstov SA, Minayeva OV, Kulikov OA, Chervyakova NN, Medvezhonkov VYu. Targeted delivery of doxorubicin by exogenous biocompatible nanovektors in experimental neoplasia. Vestnik Mordovskogo universiteta = Mordovia University Bulletin. 2017; 1(27):93-107. DOI: 10.15507/0236-2910.027.201701.093-107
Contribution of the co-authors: A. Zaborowskiy reviewed relevant literature, synthesized DNA-Dox conjugates, investigated the acute toxicity of DNA-Dox conjugates and antitumor activity of DNA-Dox conjugate, processed statistics, wrote the draft; A. Kokorev analyzed literary sources, synthesized DNA-Dox conjugates, investigated the antitumor activity of DNA-Dox conjugates, wrote the draft; Ye. Brodovskaya investigated the acute toxicity of DNA-Dox conjugates and antitumor activity of DNA-Dox conjugates; S. Firstov transplanted tumors, investigated the antitumor activity of the conjugate DNA Docks; O. Minayeva analyzed literary data, investigated the acute toxicity of DNA-Dox conjugate, processed statistics, wrote the draft; A. Kulikov transplanted tumors, investigated the antitumor activity of DNA-Dox conjugate; N. Chervyakova investigated the acute toxicity of DNA-Dox conjugate and anti-tumor activity of DNA-Dox conjugate; V. Medvezhonkov investigated the acute toxicity of DNA-Dox conjugate.
All authors have read and approved the final manuscript.
This work is licensed under a Creative Commons Attribution 4.0 License.
