Polymeric iron chelators for enhancing 5‐aminolevulinic acid‐induced photodynamic therapy

Abstract

5-Aminolevulinic acid (5-ALA) is an amino acid that can be metabolized into a photosensitizer, protoporphyrin IX (PpIX) selectively in a tumor cell, permitting minimally invasive photodynamic diagnosis/therapy. However, some malignant tumor cells have excess intracellular labile iron and facilitate the conversion of PpIX into heme, which compromises the therapeutic potency of 5-ALA. Here, we examined the potential of chelation of such unfavorable intratumoral labile iron in photodynamic therapy (PDT) with 5-ALA hydrochloride, using polymeric iron chelators that we recently developed. The polymeric iron chelator efficiently inactivated the intracellular labile iron in cultured cancer cells and importantly enhanced the accumulation of PpIX, thereby improving the cytotoxicity upon photoirradiation. Even in in vivo study with subcutaneous tumor models, the polymeric iron chelator augmented the intratumoral accumulation of PpIX and the PDT effect. This study suggests that our polymeric iron chelator could be a tool for boosting the effect of 5-ALA-induced PDT by modulating tumor microenvironment.

The Involvement of Ascorbic Acid in Cancer Treatment

“…Iron chelators boost PDT sensitization, potentially destroying tumor cells by binding iron within cancer cells (mouse colon cancer cells and human gastric cancer cells) and forming active compounds. This process leads to the generation of reactive oxygen species, further augmented by VC [81]. In cancer photothermal therapy, VC is primarily used in conjunction with photothermal materials and nanoparticles for treatment.…”

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro

“…It has been demonstrated that CP94 is more effective at increasing PpIX build-up compared to other iron chelators, such as deferoxamine (DFO) and ethylenediaminetetraacetic acid (EDTA) [ 19 ]. However, to our knowledge, it is yet to be evaluated in comparison to the new polymeric DFO iron-chelating agent that has recently been developed [ 20 ].…”