Targeted delivery of doxorubicin by exogenous biocompatible nanovektors in experimental neoplasia

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-conju-gated 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.