Synthesis of water-soluble protoporphyrin IX polymers and their photodynamic application

Protoporphyrin IX (PpIX) is a photosensitizer used in photodynamic therapy, however, its poor aqueous solubility always presents challenges and limits its application. To solve these problems water-soluble derivatives of PpIX were synthesized by esterification with polyethylene glycol, and polymerization of the PpIX diol with hexamethylene diisocyanate to form a water-soluble polyurethane. The polyurethane PpIX derivatives were characterized and showed high levels of singlet oxygen generation. The photodynamic antibacterial activity of the PpIX derivatives were explored on Escherichia coli, Staphylococcus aureus and methicillin-resistant Staphylococcus aureus indicated that 100% antibacterial killing was achieved with a concentration of 40 mu M upon 405 nm irradiation for 5 min. The polyurethane showed high biocompatibility in the dark with a variety of cell lines, but when exposed to 405 nm light (for 5 min) cytotoxic singlet oxygen was generated, resulting in cell death. Importantly, this was also possible with 635 nm illumination. In summary this novel protoporphyrin polyurethane overcomes the issues of solubility, and offers enhanced killing (singlet oxygen) generation with the potential to be used in photodynamic therapy for both antibacterial and anticancer treatment.