DNA-Programmed Control of Photosensitized Singlet Oxygen Production

Abstract

DNA sequence-controlled on-and-off switching of a singlet oxygen sensitizer has been developed and demonstrated. The singlet oxygen photosensitizer pyropheophorbide-a (P) was attached to a 15-mer nucleotide sequence. A molecule that could quench the sensitizer, the so-called "black hole quencher 3" (Q), was attached to a complementary nucleotide strand. Upon hybridization of the two conjugates, singlet oxygen production from P was completely shut down. Upon the addition of a third DNA sequence that can displace and release the P-DNA conjugate from the P-Q pair, up to 85% of the singlet oxygen production was recovered. This system is a model for a benign drug that becomes active only in the presence of a specific targeted nucleotide sequence.

New Singlet Oxygen Donors Based on Naphthalenes: Synthesis, Physical Chemical Data, and Improved Stability

“…Although the PDT features good results, it is limited by a number of problems, such as the non‐transparency of human tissue 15. Thus, optical fibers16 can be used or sensitizers with two photon absorption in the IR region 7a. 17 An attractive alternative is the thermal release of 1 O 2 from endoperoxides 2 derived from the sensitized photooxygenation of acenes 1 (Scheme ) 18.…”

Regulation of Singlet Oxygen Generation Using Single-Walled Carbon Nanotubes

“…Several research groups have now taken this approach to develop selective PDT agents that can be triggered by protease digestion, 3 pH change, 4 or DNA hybridization. 5 For instance, Zhang and coworkers 3b have reported a photodynamic molecular beacon, in which a photosensitizer and a 1 O 2 quencher were kept in close proximity by a disease-specific peptide sequence. Upon enzyme cleavage, the photosensitizer was freed from the quencher, leading to an increase in the amount of SOG.…”

Model Systems for Activation of Nucleic Acid Encoded Prodrugs

“…[22] A great deal of research activity has focused on the role that singlet oxygen plays in mechanisms of photoinduced cell death. [23] Photoinduced singlet oxygen mediated cell death is the foundation upon which photodynamic therapy (PDT) is based.…”

“…[24] PDT is now an acknowledged treatment for a number of maladies including some cancers and macular degeneration. [25] In their proof-of-principle study, [22] the chromophore pyropheophorbide-a (P), known to proficiently photosensitize the production of singlet oxygen upon energy transfer from its triple excited state, [26] was conjugated to the 5' terminal of a 15-mer DNA sequence (Scheme 6). On another complementary 21-mer DNA sequence the so-called "Black Hole Quencher 3" (Q) was attached at the 3' terminal.…”