In vitro antitumor activity of the folate-bound intracellular pH-sensitive polymeric micelle drug carriers for tumor-targeted cancer treatment

A multifunctional intracellular pH-sensitive polymeric micelle carrier whose surface was conjugated with folic acid for active drug delivery was prepared and characterized in this study. Self-assembling amphiphilic block copolymers, folate-poly(ethylene glycol)-poly (aspartate hydrazone adriamycin) [Fol-PEG-P(Asp-Hyd-ADR)], were synthesized to prepare the micelles by developing a new synthetic method. Prepared micelle had an approximately 60 nm diameter. It is notable that a folate molecule was conjugated to the end of the shell-forming PEG chain while anticancer drugs, adriamycin (ADR) were bound to the side chain of the core-forming segment through an acid-sensitive hydrazone bond so that the micelle can selectively release the loaded ADR under intracellular acidic environment (pH 5-6) after folate-mediated intracellular trafficking. Obtained experimental results revealed that these micelles significantly improved cell growth inhibitory activity in spite of a short exposure time probably due to the selective and strong interaction between folate molecules and their receptors on the cell.