Methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) block-graft copolymers with pendant fluorescent groups: synthesis, characterization and cellular uptake

Block-graft methoxy poly(ethylene glycol)-b-poly(epsilon-caprolactone) copolymers with pendant fluorescent pyrene groups were synthesized by post-polymerization conjugation of 1-pyrenemethyl 4-pentynoate (PMP) onto azido-functionalized MPEG-b-P alpha N3CL using the "click" reaction. Copolymers were characterized by differential scanning calorimetry (DSC), H-1 NMR, IR, and gel permeation chromatography. The block-graft copolymers formed micelles in the aqueous phase, with critical micelle concentrations (CMCs) in the range of 2.9-19.4 mgL(-1). Transmission electron microscopy (TEM) was used to analyze micelle morphology, and it revealed a spherical structure. The mean hydrodynamic diameters of the micelles from dynamic light scattering were in the range of 38-96 nm. In vitro cell viability assay indicated that MPEG-b-(P alpha N3CL-g-PMP/alkyne) has low cytotoxicity. Doxorubicin hydrochloride (DOX)-loaded micelles facilitated human cervical cancer (HeLa) cell uptake of DOX; uptake was completed within 4 h, and DOX was able to reach intracellular compartments and enter nuclei by endocytosis.