Block copolymers of Pluronics and poly-(2-dimethylamino+ethyl methacrylate) for delivery of oligonucleotides into tumor cells

Poly-(2-dimethylaminoethylmethacrylate) (pDMAEMA) and its block copolymers with Pluronics L61, P85 and F127 were synthesized via controlled atom-transfer radical polymerization (ATRP) using 2-bromopropionyl groups as initiators. Being a weak polycation, pDMAEMA contains only 10-20% of charged repeat units at pH 7.0. Therefore, complete binding of a short 11-mer oligonucleotide was achieved only at 5-10-fold excess of pDMAEMA repeat units as against oligonucleotide phosphate groups. Ability of the copolymers to favor penetration of the oligonucleotide into immortalized NIH/3T3 mouse fibroblasts transfected with the EWS-Fli1 cDNA under the control of the LTR retroviral promoter, which mimic spontaneous transformations occurring in patients with Ewing sarcomas, was investigated. It was found that the copolymers facilitated the penetration of the oligonucleotide into the cell nuclei with the efficacy increased in the series P85-pDMAEMA