Development of ethylene oxide and propylene oxide copolymer based nanoparticles for enhancing analysis and intracellular delivery of some biologically active substances

Owing to their unique physicochemical and biological properties ethylene oxide and propylene oxide block copolymers (Pluronics) are of considerable interest in the field of development of biocompatible materials and especially new drug delivery systems. Present work is dedicated to the construction of Pluronic-based nanoparticles for intracellular delivery of low molecular weight drugs and SERS analysis of biomolecules and living cells.So far, very little is known about the effect of polymer structure and introduction of chemical groups on biological properties of Pluronics. In this study Pluronics of different structure were modified with terminal carboxylic groups. According to cytotoxicity study, modified Pluronics were much less toxic for human cells than unmodified polymers. At the same time, introduction of carboxylic group did not affect the ability of Pluronic to increase cytotoxicity of anticancer drug doxorubicin towards MDR human cells. We ascertained an effect of modified Pluronics on cellular ATP level and membrane fluidity as well as localization of doxorubicin-Pluronic complexes inside the cells. On the basis of our results, some probable mechanisms of pharmacological effects of Pluronics were proposed.In order to fabricate SERS probes citrate-stabilized silver nanoparticles were modified with a thin layer of Pluronics of different structure. Such a modification resulted in significant amplification of SERS signal of certain fluorescent dyes and metabolites of aromatic nature probably due to the promotion of their interaction with the probe. Polymer-modified nanoparticles were applied for SERS detection rhodamine 6G released from cells into surrounding medium and certain cellular metabolites which presumably correspond to adenine nucleotides. The results obtained in this study are of particular interest for the development of informative SERS assays for analysis of drugs, fluorescent dyes and cellular metabolites.