Self-quenchable biofunctional nanoparticles of heparin–folate-photosensitizer conjugates for photodynamic therapy

Novel amphiphilic polysaccharide/PS conjugates synthesized by chemical conjugation of heparin with a hydrophobic photosensitizer (PS), pheophorbide a (PhA), and a targeting ligand, folate, were investigated for their potential application in photodynamic therapy (PDT). The anticoagulant activity of heparin-PhA (HP) and folate–heparin–PhA (FHP) conjugates was significantly decreased compared to that of heparin, thereby potentially reducing the hemorrhagic side effects. The critical self-quenching concentrations of the conjugates were decreased as the content of PhA rose. HP and FHP conjugates formed nano-sized particles in aqueous medium through a self-assembling process, and the nanoparticles were 130–170 nm in size, with a unimodal pattern of size distribution. Photoactivity of HP and FHP nanoparticles was evaluated by measuring the generation of singlet oxygen in DMF and PBS. The nanoparticles displayed a self-photoquenching effect in PBS, while the generation of singlet oxygen dramatically increased in DMF. HP and FHP nanoparticles exhibited marked phototoxicity on HeLa cells and were minimally dark-toxic without light treatment.