Concentration Control of Chemosensitizing, Cell Protectiveness, and Cytotoxic Properties of Pluronics

To elucidate factors stirring the manifestation of different biological effects of Pluronics, we exposed multidrug resistant NCI/ADR-RES cells to various concentrations of polymers in the absence or presence of 5 mu g/mL of doxorubicin. This method of analysis showed that each Pluronic exhibits chemosensitizing, cell supporting, and cytotoxic properties depending on its concentration. The effects developed in certain concentration ranges specific to each polymer. The free energies of Pluronics interaction with the lipids of cell membrane determined from the concentration dependencies of MDR suppression were close to the free energies of Pluronics partitioning between water and lipid bilayer of liposomes, indicating that PPO-lipid interaction underlies MDR suppression. Free energies corresponding to the increase in cell viability correlated with Pluronic's binding to cells. It follows that cell support by Pluronics results from their attachment to the cell surface. The presented data are feasible for predicting the biological properties of PEG-containing block copolymers.