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A polymeric micelle, based on the poly(benzyl-L-histidine)-b-poly(ethylene glycol) (polyBz-His-b-PEG) diblock copolymer, was designed as a tumor-specific targeting carrier. The micelles (particle size: 67-80 nm, critical micelle concentration (CMC); 2-3 μg/mL) were formed from the diafilteration method at pH 7.4, as a result of self-assembly of the polyBz-His block at the core and PEG block on the shell. Removing benzyl (Bz) group from polyBz-His block provided pH-sensitivity of the micellar core; the micelles were physically destabilized in the pH range of pH 7.4-5.5, depending on the content of the His group free from Bz group. The ionization of His group at a slightly acidic pH promoted the deformation of the interior core. These pHdependent physical changes of the micelles provide the mechanism for pH-triggering anticancer drug (e.g., doxorubicin: DOX) release from the micelle in response to the tumor’s extracellular pH range (pH 7.2-6.5).

Poly(benzyl-L-histidine)-b-Poly(ethylene glycol) Micelle Engineered for Tumor Acidic pH-Targeting, in vitro Evaluation