N‐Boc‐Histidine‐Capped PLGA‐PEG‐PLGA as a Smart Polymer for Drug Delivery Sensitive to Tumor Extracellular pH

Abstract A pH‐sensitive polymer was synthesized by introducing the N ‐Boc‐histidine to the ends of a PLGA‐PEG‐PLGA block copolymer. The synthesized polymer was confirmed to be biodegradable and biocompatible, well dissolved in water and forming micelles above the CMC. DOX was employed as a model anticancer drug. In vitro drug release from micelles of N ‐Boc‐histidine‐capped PLGA‐PEG‐PLGA exhibited significant difference between pH = 6.2 and pH = 7.4, whereas DOX release from micelles composed of un‐capped virgin polymers was not significantly sensitive to medium pH. Uptake of DOX from micelles of the new polymer into MDA‐MB‐435 solid tumor cells was also observed, and pH sensitivity was confirmed. Hence, the N ‐Boc‐histidine capped PLGA‐PEG‐PLGA might be a promising material for tumor targeting. magnified image