Light-Controlled Release of Water-Soluble Photosensitizers from a Biocompatible Polymer Based on Polyallylamine Functionalized with Folic Acid

Abstract

We have synthesized a photoactive polymer capable of releasing, upon irradiation, fluorescent compounds with photosensitizing properties. Folic acid (PteGlu), a vitamin of the folate family, was covalently attached to polyallylamine (PAH), a biocompatible polymer. The functionalization was optimized to obtain a substitution degree of approximately 1% with 50% of conversion in less than 2 h of reaction time. The resulting modified polymer (PAH-PteGlu) was purified by size exclusion chromatography and characterized by NMR to confirm covalent binding. A detailed study of physicochemical and photochemical properties was carried out after functionalization. PAH-PteGlu is highly soluble and stable not only in water but also in acidic conditions. This is a significant improvement over its parent molecule, folic acid, which becomes insoluble at low pH. Upon excitation with UVA radiation (320–400 nm) in air-saturated aqueous solutions, the attached PteGlu underwent cleavage and oxidation, yielding H₂O₂ and 6-formylpterin (Fop), which, in turn, photooxidized to 6-carboxypterin (Cap). In this photochemical process, the pterin moiety was released, whereas the p-aminobenzoylglutamic acid (PABA-Glu) portion remained attached to PAH. To explore the functionality of PAH-PteGlu as a vehicle for photodynamic therapies (PDT), the photosensitizing properties were evaluated using the nucleoside 2′-deoxyguanosine (dG) as a model of oxidizable biological target. The nucleoside was consumed upon irradiation in the presence of PAH-PteGlu. However, dG was not photosensitized directly by PAH-PteGlu, but by Fop and Cap, released in the photolysis of PAH-PteGlu.