DescriptionThe efficiency of siRNA is limited by its low resistance against enzymatic degradation, limited permeability across cell membrane, and substantial liver and renal clearance. Therefore, in order to exploit potential therapeutic applications of siRNA, the effective delivery of siRNA to the site of action and into targeted cells is required. We are proposing to design, characterize and taste in vitro the efficient siRNA delivery systems in order to treat human ovarian carcinoma. Internally quaternized poly(amidoamine) dendrimer (PAMAM) with different surface modifications and poly(amidoamine)-poly(ethylene glycol)-poly-L-lysine conjugates were prepared and successfully delivered siRNA into A2780 ovarian cancer cells. To effectively treat primary ovarian tumor, prevent the development of intraperitoneal metastases and limit side effects of therapy, we proposed a combination of receptor-mediated targeted chemotherapy with genotherapy. To this end, we used tumor-targeted complex liposomal delivery systems containing: (1) two anticancer drugs with different mechanisms of action (doxorubicin and cisplatin); (2) suppressors of two different mechanisms of cellular resistance - two antisense oligonucleotides (ASO) targeted to MDR1 and BCL2 mRNA; and (3) a targeting moiety specific to cancer cells – LHRH peptide (ligand specific to LHRH receptors that are overexpressed in plasma midbrain of ovarian cancer cells). The targeted combinatorial treatment of primary aggressive ovarian tumor led to the substantial regression of the growth of primary tumor, prevention of the development of intraperitoneal metastases and limitation of the adverse side effects of chemotherapy on healthy organs.