Zwitterionic Reduction-Activated Supramolecular Prodrug Nanocarriers for Photodynamic Ablation of Cancer Cells.

ABSTRACT

An adamantane-containing zwitterionic copolymer poly(2-(methacryloyloxy)ethyl phosphorylcholine)- co-poly(2-(methacryloyloxy)ethyl adamantane-1-carboxylate) (poly(MPC- co-MAda)) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The hydrophobic photosensitizer chlorin e6 (Ce6) was conjugated to ß-cyclodextrin (ß-CD) by glutathione (GSH)-sensitive disulfide bonds. The Ce6 conjugated supramolecular prodrug nanocarriers were fabricated due to the host-guest interaction between adamantane and ß-CD, which was confirmed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The Ce6 conjugated prodrug nanocarriers showed reduction-responsive release of Ce6, which could result in the activation of Ce6. The generation of cytotoxic reactive oxygen species (ROS) was significantly enhanced due to the activation of Ce6. In additiona, the Ce6 conjugated prodrug nanocarriers could effectively inhibit the proliferation of cancer cells upon light irradiation.