Heparin-based self-assembled nanoparticles for photodynamic therapy

Novel heparin-based self-assembled nanoparticles were developed for photodynamic cancer therapy. A heparin-poly(beta-benzyl-L-aspartate) (HP) amphiphilic copolymer was synthesized for effective delivery of a hydrophobic photosensitizer, pheophorbide a (Pheo). The anti-coagulant activity of the HP copolymer decreased significantly, as measured by an anti-FXa chromogenic assay. Pheo was effectively incorporated into the HP nanoparticles using a dialysis technique. A good drug-loading content was obtained by altering the composition of the HP copolymer and Pheo/HP feed ratio. The Pheo-loaded HP nanoparticles had an average diameter of 117-189 nm, a negatively charged surface, and a sustained drug release pattern. These properties may allow them to passively target the tumor site through an enhanced permeability and retention (EPR) effect. Furthermore, the Pheo-loaded HP nanoparticles demonstrated marked photocytotoxicity and minimal darktoxic without a light treatment. The 6HP-Pheo15 nanoparticles were internalized into SCC7 cancer cells and damaged the cells after a light treatment. This suggests that HP nanoparticles have potential as an effective delivery system for clinical PDT.