Direct Conjugation of TiO₂ Nanoparticles with Phototherapeutic Prodrug 5‐Aminolevulinic Acid

Abstract TiO₂ nanoparticles (TiO₂NPs) were directly conjugated with the phototherapeutic prodrug, 5‐aminolevulinic acid (ALA), using a mild and green approach. The resultant TiO₂NPs‐ALA nanoconjugates were characterized by different techniques, including HPLC, UV‐Vis, FTIR‐ATR, ¹H‐NMR, FESEM‐EDS, TEM, DLS, and synchrotron radiation‐induced XPS (SR‐XPS) to assess the successful loading of 15 % and the chemical stability of ALA on the TiO₂NPs. More importantly, the SR‐XPS results showed the stabilizing effect of TiO₂ nanosurface on the ALA molecules (against structural change) in neutral and alkaline pHs, which is of great significance in the potential therapeutic applications of ALA. The FESEM and TEM results exhibited the grain‐like TiO₂NPs‐ALA particles with a 20–50 nm size distribution, indicating size‐controlling effect of ALA on the TiO₂NPs during the conjugation process and the presence of the organic molecule layer onto the surface. TiO₂NPs‐ALA represents a promising candidate for studies in photodynamic therapy considering the stabilization effect observed by spectroscopic characterizations.