Enhancement of photodynamic antitumor effect with pro‐oxidant ascorbate

Abstract

Photodynamic therapy (PDT) is a treatment modality that utilizes photosensitizers activated by light to induce cell death via the formation of singlet oxygen and other free radicals. Although this method has its advantages for tumor treatment, it cannot be well performed for involving so many therapeutic parameters during use. Tumor recurrence is common due to insufficient treatment. Therefore, a supplemental or complemental treatment is necessary for PDT. L-ascorbate, commonly known as vitamin C, is an essential nutrient for humans. It is also a well-established pro-oxidant in the presence of certain transition metal ions. In our experiments, ascorbate was administered to tumor-bearing mice by intraperitoneal injection (i.p.) for 10 days after they were treated with PDT. We hypothesize that this supplement may improve the therapeutic outcome by as a result of the reactions between ascrobate and the metal ions induced by PDT. The results demonstrate that PDT can cause Fe and Cu ions to be released from their protein complexes. The reactions between the ions and ascorbate resulted in a post-PDT surge in reactive oxygen species (ROS) as demonstrated in vitro with chemiluminescence detection. This ultimately leads to enhanced tumor cell death and, thus, an improved treatment outcome. Based on the results that PDT induces metal ion release and ascorbate reacts with the metal ions producing subsequent ROS, an internal related, complementary and strengthened tumor treatment is established by combination of both PDT and ascorbate, as a low-toxicity and effective method.