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Reactive oxygen-dependent production of novel photochemotherapeutic agents
1Department of Physiology, National University of Singapore, Singapore 117597. phssp@nus.edu.sg
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.
Insights
Preactivation uses light to activate photosensitizers, creating novel therapeutic agents. This bypasses the need for simultaneous light and drug exposure, offering a new approach to photochemotherapy.
Area of Science:
- Biochemistry
- Photochemistry
- Oncology
Background:
- Reactive oxygen species (ROS) like singlet oxygen and hydrogen peroxide are used in photodynamic therapy (PDT) to target diseased cells.
- Conventional PDT requires simultaneous exposure to light and photosensitizers, limiting its clinical application.
- Preactivation, developed in 1990, circumvents this limitation by pre-exposing photosensitizers to light.
Purpose of the Study:
- To review the role of ROS in photodynamic effects.
- To explain the mechanism of preactivation.
- To propose preactivation as a novel method for generating biologically active molecules and potentially explain PDT mechanisms.
Main Methods:
- Review of existing literature on photodynamic therapy and reactive oxygen species.
- Explanation of the preactivation mechanism.
- Discussion of chromophores like merocyanine 540, Photofrin II, and naphthalimide used in preactivation.
Main Results:
- Preactivation allows for the generation of biologically active molecules in vitro.
- Photo-oxidation of sensitizers generates novel active compounds.
- This process may also contribute to the mechanism of conventional PDT.
Conclusions:
- Preactivation offers a novel strategy for producing photochemotherapeutic agents.
- The mechanism of preactivation involves light-induced generation of active molecules.
- Understanding chromophore breakdown is key to both preactivation and conventional PDT.