Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer

Kyoung-Ran Kim (1) , Pascal Röthlisberger (2) , Seong Jae Kang (1) , Kihwan Nam (1) , Sangyoup Lee (1) , Marcel Hollenstein (2) , Dae-Ro Ahn (1, 3)

1 KISTI - Korea Institute of Science and Technology Information
2 Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids
3 UST - University of Science and Technology [Daejeon]

Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance. Here, we showed that the DNA nanoparticles (DNPs) can be prepared with RCA and modified nucleotides that have side-chains appended on the nucleobase are capable of interacting with the DNA strands of the resulting RCA products. The incorporation of the modified nucleotides improved cellular uptake efficiency and nuclease resistance of the DNPs. We also demonstrated that these DNPs could be employed as carriers for the delivery of a photosensitizer into cancer cells to achieve photodynamic therapy upon irradiation at both the in vitro and in vivo levels.

Mots clés: DNA nanoparticles; modified nucleotides; photodynamic therapy; photosensitizer; rolling circle amplification

Domaines: Chimie; Chimie organique

Kyoung-Ran Kim, Pascal Röthlisberger, Seong Jae Kang, Kihwan Nam, Sangyoup Lee, et al.. Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer. Molecules, 2018, Special Issue Oligonucleotides Application to Nano- and Biotechnology (DNA Origami, DNA Machine), 23 (7), pp.1833. ⟨10.3390/molecules23071833⟩. ⟨pasteur-02012256⟩