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

摘要

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