Authors: V.E. Orel, A.D. Shevchenko, N.A. Nikolov, N.N. Dzyatkovskya, A.V. Romanov, A.Yu. Richalskiy, A.P. Burlaka, S.M. Lukin, V.N. Uvarov, I.B. Schepotin
Affilation: National cancer institute, Ukraine
Pages: 388 - 391
Keywords: nanoparticles, iron oxide, Lewis lung carcinoma
Introduction. Current forms of antitumor anthracycline antibiotic doxorubicin (DOXO) are highly toxic to the patient and can cause systematic complications, most notably cardiotoxicity. Systemic toxicity can seriously decrease the effectiveness of the drug since a lower dose must be administrated to avoid toxicity. Drug resistance is the single most important cause of cancer treatment failure and carries a massive burden to patients, healthcare providers, drug developers and society. Thus, problems related to the development multidrug resistance have led researchers to investigate alternative forms of nanocomplex from nanoparticles and DOXO for treatment of cancer. This paper examines the effects of nanocomplex from nanoparticles iron (II,III) oxide and DOXO on nonlinear dynamics of the growth during treatment by of Lewis lung carcinoma. Materials and methods. Mechanochemical synthesis (MS) and mechanomagnetochemical dry synthesis (MMS) of DOXO (Pfizer, Italy) with nanoparticles ferric oxide in nanocomplex (NC) were processed in original high-precision mechanomagnetoreactor (NCI, Ukraine). In the study 40 C57BL/6 male mice weighing 19 ± 1 g bred in the vivarium of National Cancer Institute (Kyiv, Ukraine) were used. Animals were housed in 4 groups: group 1 – control (no treatment); 2 –MS NC-administration; 3 – MMS NC –administration; 4 – conventional DOXO–administration. Nonlinear kinetics of tumor volume was evaluated by growth factor according to autocatalytic equation. Statistical processing of numerical results was carried out using Statistica 6.0 (© StatSoft, Inc. 1984–2001) computer program with parametric Student’s t-test. Results and discussion. Our study shows that the growth kinetics of Lewis lung carcinoma and dissemination of tumor are dynamically similar to chaotic (nonlinear) processes. Growth factor for tumor volumes on 12 and 17th day after tumor transplantation was maximal and braking ratio was minimal after treatment by MMS NC (3 groups animals). Since 17th day after transplantation tumor volumes for animals from 3 groups this tendency was similarly. The most significant antimetastatic tendency has been registered after treatment by MMS NC. What is the interrelation between the physicochemical and antitumor effects? We suppose that MMS NC stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being resealed and thereby stopping the process of replication. Conclusion In the research of animals with Lewis lung carcinoma was shown, that mechano- magnetochemically synthesized nanocomplex on the basis of nanoparticles from iron (II,III) oxide and doxorubicin had a greater antitumor effect than conventional doxorubicin.