Kazutaka Hirakawa

By Kazutaka Hirakawa

Part of the book: Smart Nanoparticles Technology

By Kazutaka Hirakawa

Titanium dioxide (TiO2), a semiconducting material, is a well-known photocatalyst. A nanoparticle (NP) of TiO2 also demonstrates photocatalytic activity. Photo-irradiated TiO2 NPs induce the formation of various reactive species, leading to the damage of biomacromolecules. These reactive species include h+, either free or trapped hydroxyl radicals (OH⋅), superoxide (O2⋅-), hydrogen peroxide (H2O2), and singlet oxygen (1O2), among others. TiO2 NPs photocatalyze DNA oxidation. A relatively small concentration of TiO2 NPs frequently induces tandem base oxidation at guanine and thymine residues through H2O2 generation in the presence of a copper(II) ion. A copper–peroxo complex is considered to be an important reactive species responsible for this DNA damage. In the case of a high concentration of TiO2 NPs, OH⋅ contributes to DNA damage without sequence specificity. In the presence of sugars, TiO2 NPs indirectly induce DNA damage by the secondary H2O2, which is produced through an autoxidation process of the product of sugar photooxidized by TiO2 NPs. Furthermore, 1O2 is also produced by photo-irradiated TiO2 NPs. The photocatalyzed formation of 1O2 might contribute to the oxidation of the membrane protein. These mechanisms of photocatalytic formation of the reactive species may be involved in the photocytotoxicity of TiO2 NPs.

Part of the book: Nanoparticles Technology

By Kazutaka Hirakawa

The purpose of this chapter is the brief review of the fundamental study of porphyrin “theranostics” by DNA. Porphyrins have been studied as photosensitizer for photodynamic cancer therapy. The activity control of fluorescence emission and photosensitized singlet oxygen generation by porphyrins using the interaction with DNA is the initial step in achieving theranostics. To control these photochemical activities, several types of electron donor‒connecting porphyrins were designed and synthesized. The theoretical calculations speculated that the photoexcited state of these porphyrins can be deactivated via intramolecular electron transfer, forming a charge‒transfer state. The electrostatic interaction between the cationic porphyrin and DNA predicts a rise in the energy of the charge‒transfer state, leading to the inhibition of electron transfer quenching. Pyrene‒ and anthracene‒connecting porphyrins showed almost no fluorescence in an aqueous solution. Furthermore, these porphyrins could not photosensitize singlet oxygen generation. These porphyrins bind to a DNA groove through an electrostatic interaction, resulting in the increase of fluorescence intensity. The photosensitized singlet oxygen‒generation activity of DNA‒binding porphyrins could also be confirmed. On the other hand, several other porphyrins could not demonstrate the activity control properties. To realize effective activity control, a driving force of more than 0.3 eV is required for the porphyrins.

Part of the book: Phthalocyanines and Some Current Applications

By Kazutaka Hirakawa

Hydrogen peroxide (H2O2) and singlet oxygen (1O2) are important reactive oxygen species (ROS) for biological and medicinal fields. Oxidation processes of chemical materials by molecular oxygen are important H2O2 source, whereas photochemical reaction is important for 1O2 production. Reactivity and biomolecule damage by these ROS depend on the surrounding conditions and targeting molecules. In this chapter, production mechanisms of H2O2 and 1O2, biomolecule oxidation by these ROS, their detection methods, and production control of 1O2 are briefly reviewed.

Part of the book: Reactive Oxygen Species (ROS) in Living Cells

By Kazutaka Hirakawa

Photodynamic therapy (PDT) is a less-invasive treatment of cancer and precancerous lesions. Porphyrin derivatives have been used and studied as the photosensitizers for PDT. In general, the biomacromolecules oxidation by singlet oxygen, which is produced through energy transfer from the photoexcited photosensitizers to oxygen molecules, is an important mechanism of PDT. However, the traditional PDT effect may be restricted, because tumors are in a hypoxic condition and in certain cases, PDT enhances hypoxia via vascular damage. To solve this problem, the electron transfer-mediated oxidation of biomolecules has been proposed as the PDT mechanism. Specifically, porphyrin phosphorus(V) complexes demonstrate relatively strong photooxidative activity in protein damage through electron transfer. Furthermore, other photosensitizers, e.g., cationic free-base porphyrins, can oxidize biomolecules through electron transfer. The electron transfer-supported PDT may play the important roles in hypoxia cancer therapy. Furthermore, the electron transfer-supported mechanism may contribute to antimicrobial PDT. In this chapter, recent topics about the biomolecules photooxidation by electron transfer-supported mechanism are reviewed.

Part of the book: Photodynamic Therapy