Development of folate-bound intracellular pH-sensitive polymeric micelle drug carriers for tumor-directed cancer treatment

A new type of multi-functional intracellular pH-sensitive polymeric micelle carrier system for active drug delivery was prepared and characterized in this study. Self-assembling amphiphilic block copolymers, folate-pory(ethylene glycol)-poly (aspartate hydrazone adriamycin) [Fol-PEG-P(Asp-Hyd-ADR)], were synthesized to prepare the micelles, which have approximately 60 nm diameters. A folate molecule was conjugated to the end of the shell-forming PEG chain while anticancer drugs, adriamycin were bound to the side chain of the core-forming segment through an acid-sensitive hydrazone bond that is selectively cleavable under intracellular acidic environment (pH 5-6). The selectivity of the micelles to folate-binding proteins was evaluated by surface plasmon resonance measurements, and MTT assay, using human pharyngeal cancer cell (KB cell), revealed that the micelles improved cell growth inhibitory activity significantly in spite of a short exposure time probably due to the selective and strong interaction between folate molecules and their receptors.