Synthesis and investigation of the specific activity of the DNA-doxorubicin conjugates

1st International Symposium 'Physics, Engineering and Technologies for Bio-Medicine'

医药卫生;物理学;工业技术

Kokorev, A.V.^1 ; Zaborovskiy, A.V.^2 ; Kotlyarov, A.A.^1 ; Balykova, L.A.^3 ; Malkina, M.A.^3 ; Kargina, I.V.^3 ; Gromova, E.V.^3 ; Medvezhonkov, V.Yu.^3 ; Gurevich, K.G.^2 ; Shchukin, S.A.^3 ; Pyataev, N.A.^3

National Research Nuclear University, MEPhI, Moscow, Russia^1

Moscow State University of Medicine and Dentistry Named after A. I. Yevdokimov, Moscow, Russia^2

National Research Mordovia State University, Saransk, Russia^3

关键词: Antineoplastic activity;    Chemotherapeutic agents;    Double stranded DNA;    Doxorubicin conjugates;    Lewis lung carcinomata;    Optimal conditions;    Specific activity;    Water soluble drugs;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/784/1/012026/pdf
DOI  :  10.1088/1742-6596/784/1/012026

来源: IOP

【 摘 要 】

In the present work, the method of obtaining the conjugate of the anticancer chemotherapeutic agent doxorubicin to 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. Clearing the conjugate from the non-encapsulated chemotherapeutic agent was being made by ultrafiltration method. The investigation of the toxicity and specific antineoplastic activity of the synthesized complex was conducted. The performance of the drug toxicity were 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 on mice with the transplanted Lewis lung carcinoma (LLC). It was demonstrated that the conjugate toxicity is approximately lower that the one of the unconjugated doxorubicin (LD 50 was equal 14.6 mg/kg and 9.9 mg/kg for the conjugate and doxorubicin, respectively). The specific antineoplastic activity was investigated in equitoxic doses of the drug. It was established that the conjugate being administered in equitoxic doses possesses a stronger antineoplastic activity, than the water-soluble drug (maximum 35% more as to the tumor volume and 51% more as to the Tumor Growth Inhibition index).