Singlet Oxygen in DNA Nanotechnology

Abstract

CONSPECTUS: Singlet oxygen ((1)O2), the first excited electronic state of molecular oxygen, is a significant molecule, despite its minute size. For more than half a century, the molecule has been widely used and studied in organic synthesis, due to its characteristic oxygenation reactions. Furthermore, (1)O2 plays a key role in mechanisms of cell death, which has led to its use in therapies for several types of cancer and other diseases. The high abundance of oxygen in air provides a wonderful source of molecules that can be excited to the reactive singlet state, for example, by UV/vis irradiation of a photosensitizer molecule. Although convenient, this oxygen abundance also presents some challenges for purposes that require (1)O2 to be generated in a controlled manner. In the past decade, we and others have employed DNA nanostructures to selectively control and investigate the generation, lifetime, and reactions of (1)O2. DNA-based structures are one of the most powerful tools for controlling distances between molecules on the nanometer length scale, in particular for systems that closely resemble biological settings, due to their inherent ability to specifically form duplex structures with well-defined and predictable geometries. Here, we present some examples of how simple DNA structures can be employed to regulate (1)O2 production by controlling the behavior of (1)O2-producing photosensitizers through their interactions with independent quencher molecules. We have developed different DNA-based systems in which (1)O2 production can be switched ON or OFF in the presence of specific DNA sequences or by changing the pH of the solution. To further illustrate the interplay between DNA structures and (1)O2, we present three pieces of research, in which (1)O2 is used to activate or deactivate DNA-based systems based on the reaction between (1)O2 and cleavable linkers. In one example, it is demonstrated how a blocked oligonucleotide can be released upon irradiation with light of a specific wavelength. In more complex systems, DNA origami structures composed of more than 200 individual oligonucleotides were employed to study (1)O2 reactions in spatially resolved experiments on the nanoscale.

Serum-induced degradation of 3D DNA box origami observed with high-speed atomic force microscopy

“…As a recently developed, highly efficient self-assembly technique, DNA origami is a radically increasing subgroup of DNA nanotechnologies [1][2][3][4]. By folding a long single DNA strand into arbitrary shapes with hundreds of synthetic staple strands, DNA origami forms 2D and 3D nanostructures of various degrees of complexity with high yield and accuracy [5][6][7].…”

Using photochemistry to understand and control the production of reactive oxygen species in biological environments

“…In these systems, a photosensitizer and a suitable quencher have been attached on either end of a hairpin DNA sequence or on the 5'-and 3'-end of complementary single strands DNA. [107][108][109] In these "close" conformations, 1 O 2 generation is turned "off" due to efficient RET between the photosensitizer and its quencher (vide supra) or to effective collisional quenching. [107][108][109] In the presence of external stimuli, the DNA conformation is modified keeping the photosensitizer apart from the quencher, thus enabling 1 O 2 production by the excited photosensitizer.…”

“…[107][108][109] In these "close" conformations, 1 O 2 generation is turned "off" due to efficient RET between the photosensitizer and its quencher (vide supra) or to effective collisional quenching. [107][108][109] In the presence of external stimuli, the DNA conformation is modified keeping the photosensitizer apart from the quencher, thus enabling 1 O 2 production by the excited photosensitizer. [107][108][109] Alternatively, molecules can be transformed into photosensitizers upon binding to DNA, as it has been reported for both berberine and palmatine.…”

“…[107][108][109] In the presence of external stimuli, the DNA conformation is modified keeping the photosensitizer apart from the quencher, thus enabling 1 O 2 production by the excited photosensitizer. [107][108][109] Alternatively, molecules can be transformed into photosensitizers upon binding to DNA, as it has been reported for both berberine and palmatine. [110] These two alkaloid derivatives belong to the broad family of intermolecular charge transfer (ICT) molecules, presenting both electron donating and electron withdrawing moieties.…”

Heavy atom enhanced generation of singlet oxygen in novel indenofluorene-based two-photon absorbing chromophores for photodynamic therapy

“…The photosensitizer in the triplet state can subsequently transfer its energy to the surrounding oxygen in the ground state ( 3 O 2 ), resulting in generation of singlet oxygen ( 1 O 2 ) [4,5]. Singlet oxygen is a highly reactive oxygen species that can damage biological cell components such as lipids [6], nucleic acids [7,8], or proteins [9,10]. In current PDT, one of the main problems is the limited penetration of visible light into tissue, restricting PDT to the treatment of ailments on tissue surface [11].…”