Reactive oxygen‐dependent production of novel photochemotherapeutic agents

Abstract

The reactive nature of species derived from oxygen, such as singlet oxygen and hydrogen peroxide, has been exploited in the clinical setting for targeting bacteria, viruses, and tumor cells by photodynamic excitation of a variety of chromophores. This modality, termed photodynamic therapy (PDT), is currently being used to treat some forms of cancer. However, the applicability of conventional PDT is limited due to the absolute dependence on simultaneous exposure of the target to the photoactive compound and light. In 1990, we demonstrated that the need for simultaneous exposure of the biological target to light and photosensitizer could be circumvented by prior exposure (activation) of the sensitizer molecule to light and its subsequent use as any other anti-cancer or anti-viral drug. By dint of the nature of the protocol, this process was termed preactivation. Since then, the generation of biologically active molecules in vitro by preactivation has been validated using a variety of chromophores, such as merocyanine 540, Photofrin II, and naphthalimide. Here we briefly review the role of reactive oxygen species in the photodynamic effect, and provide an explanation for the mechanism of preactivation. We propose that photo-oxidation not only provides a novel means for the generation of biologically active molecules, but could also explain, at least in part the mechanism of conventional PDT. It is likely that the light-dependent breakdown of the chromophore to generate novel active compounds, in addition to reactive oxygen species, also contributes to the photodynamic damage observed on simultaneous exposure of the chromophore and target tissue to light during PDT.-Pervaiz, S. Reactive oxygen-dependent production of novel photochemotherapeutic agents.

The mitochondrial effects of novel apoptogenic molecules generated by psoralen photolysis as a crucial mechanism in PUVA therapy

“…11 The effect of the exposure to light of a photosensitizer prior its use in biological systems was also referred to as "preactivation" by Gulliya et al [12][13][14] In the case of photoactive compounds that were irradiated with visible light, such as merocyanine 540, naphthalimide, and Photofrin II, the "preactivation" protocol was successfully exploited for antiviral and antitumor therapeutic approaches. [15][16][17][18] Here we show that POPs caused apoptosis in Jurkat cells, thus highlighting the relevance of long-lasting toxic molecules generated by psoralen photodegradation. 9 The apoptogenic potency of the mixture was reduced-but not suppressed-by irradiating the psoralen solution in the absence of oxygen, suggesting that both oxygen-dependent and oxygen-independent reactions are relevant during the process of POP generation.…”

Targeted photodynamic therapy with multiply‐loaded recombinant antibody fragments

“…This ultimately leads to the conversion of molecular oxygen into reactive oxygen species (ROS), primarily singlet oxygen, leading to tumor cell death via irreversible damage to cellular components such as proteins, lipids and DNA. 2 Current clinical use of PDT achieves efficacies similar to conventional therapies but with lower morbidity, simplicity of use and improved functional and cosmetic outcome. 3,4 PDT has mainly been used where conventional approaches have failed or were unsuitable.…”

Use of Merocyanine 540 for Photodynamic Inactivation of Staphylococcus aureus Planktonic and Biofilm Cells

“…When a PS is irradiated with light of an appropriate wavelength and at a certain level, the molecule becomes excited and consequently experiences a series of molecular energy transfers. These energy transfers lead to the liberation of cytotoxic singlet oxygen from the photosensitizer, which is lethal to many different bacteria (14).…”