Pheophorbide a-Conjugated pH-Sensitive Nanoparticle Vectors for Highly Efficient Photodynamic Therapy of Cancer

Abstract

To achieve a tumor-targeted drug delivery system for photodynamic therapy, we designed ligand-mediated nanoparticles with stable formulations of a hydrophobic photosensitizer. Folic acid (FA)-conjugated amphiphilic block copolymers of PEG and poly-β-benzyl-L-aspartate with the potential to act as pH-sensitive drug release reservoirs were synthesized. The photosensitizer was conjugated to the copolymers through pH-sensitive hydrazone (Hyd) linkages. The FA-PEG-P(Asp-Hyd)-Pheo nanoparticles had average diameters of 76–217 nm. The pH-dependent photosensitizer release property may ensure intracellular drug release inside tumor cells due to the lower pH inside the endosomes and lysosomes of tumor cells. The FA-PEG-P(Asp-Hyd)-Pheo nanoparticles demonstrated marked phototoxicity and minimal dark toxicity.