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,
Pascal Röthlisberger,
Seong Jae Kang,
Kihwan Nam,
Sangyoup Lee,
Marcel Hollenstein,
Dae-Ro Ahn
Affiliations
Kyoung-Ran Kim
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
Pascal Röthlisberger
Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, Institut Pasteur, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris CEDEX 15, France
Seong Jae Kang
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
Kihwan Nam
Center for Bionics, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
Sangyoup Lee
Center for Bionics, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
Marcel Hollenstein
Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, Institut Pasteur, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris CEDEX 15, France
Dae-Ro Ahn
Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea
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.
