Pluronic/Heparin Nanoparticles for Chemo-Photodynamic Combination Cancer Therapy through Photoinduced Caspase-3 Activation

Abstract

The Pluronic/heparin nanoparticles (NPs) were prepared for chemo-photodynamic combination cancer therapy through photoinduced caspase-3 activation. Doxorubicin (DOX) prodrug and methylene blue (MB) were assembled into a single structure by electrostatic interaction with heparin and further loaded into the NPs. MB is a photosensitizer, which can be used for photodynamic therapy, which can elicit cell death by producing reactive oxygen species (ROS). The DOX prodrug was DOX conjugated to a labile tetrapeptide (DEVD) by caspase-3 upon apoptosis. ROS was measured to verify ROS-mediated apoptosis. Membrane integrity test and flow cytometry analysis were performed to examine induced apoptosis. The tumor targeting and the in vivo antitumor efficacy were measured to evaluate chemo-photodynamic combination cancer therapy in tumor-bearing mice.