Improving photodynamic therapy efficiency by synthesis of folic acid and protoporphyrin IX conjugated persistent luminescence nanoparticles as a new drug carrier

The most challenging limitation of currently approved drugs (PpIX) for photodynamic therapy (PDT) is their absorption band located in the visible light region which limits PDT efficiency. In addition, poor water dispersion of the drugs is an obstacle preventing sufficient generation of singlet oxygen (an essential key). To provide a proper internal activating light source for PpIX, injectable persistent luminescence nanoparticles which respond to both ultraviolet (UV) and X-ray were synthesized. Then, activated PpIX was conjugated to the NPs with APTES. Finally, folic acid (FA) was covalently bonded to PpIX-conjugated NPs to improve their water dispersion and tumor targeting abilities. The size of ultimate NPs (FA-PpIX-APTES-AG NPs) was 273 ± 5.5 nm. Raman spectroscopy results confirmed not only PpIX but also FA were successfully conjugated to APTES-AG NPs. Ultimate NPs could improve the generation of singlet oxygen 2.4% more than free PpIX for concentration of 1.5 μg/ml of free PpIX. Conjugation efficiency (CE) calculation showed that in 100 μg/ml PpIX-APTES-AG NPs, there was a 2.050±0.207 μg/ml of conjugated PpIX and 100 μg/ml PpIX-APTES-AG NPs was containing 26.87±2.998 μg/ml of FA. Exposed PC3 cells to ultimate NPs (equal to 5μg/ml of free PpIX) demonstrated 30% less dark toxicity and almost 15% more toxicity after exposure to UV for 5 min compared to that of free PpIX. All mentioned results proved that the fabrication of FA-PpIX-conjugated AG NPs may introduce an acceptable solution to current challenges of PDT including weak penetration of blue light and low water dispersion of PpIX in water.