Metallointercalators-DNA Tetrahedron Supramolecular Self-Assemblies with Increased Serum Stability

M. Andrey Joaqui-Joaqui, Zoe Maxwell, Mandapati V. Ramakrishnam Raju, Min Jiang, Kriti Srivastava, Fangwei Shao, Edgar A. Arriaga, Valérie C. Pierre

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Self-assembly of metallointercalators into DNA nanocages is a rapid and facile approach to synthesize discrete bioinorganic host/guest structures with a high load of metal complexes. Turberfield’s DNA tetrahedron can accommodate one intercalator for every two base pairs, which corresponds to 48 metallointercalators per DNA tetrahedron. The affinity of the metallointercalator for the DNA tetrahedron is a function of both the structure of the intercalating ligand and the overall charge of the complex, with a trend in affinity [Ru(bpy)2(dppz)]2+ > [Tb-DOTAm-Phen]3+ ≫ Tb-DOTA-Phen. Intercalation of the metal complex stabilizes the DNA tetrahedron, resulting in an increase of its melting temperature and, importantly, a significant increase in its stability in the presence of serum. [Ru(bpy)2(dppz)]2+, which has a greater affinity for DNA than [Tb-DOTAm-Phen]3+, increases the melting point and decreases degradation in serum to a greater extent than the TbIII complex. In the presence of Lipofectamine, the metallointercalator@DNA nanocage assemblies substantially increase the cell uptake of their respective metal complex. Altogether, the facile incorporation of a large number of metal complexes per assembly, the higher stability in serum, and the increased cell penetration of metallointercalator@DNA make these self-assemblies well-suited as metallodrugs.

Original languageEnglish (US)
Pages (from-to)2928-2941
Number of pages14
JournalACS nano
Issue number2
StatePublished - Feb 22 2022

Bibliographical note

Funding Information:
The authors acknowledge support from the National Science Foundation under Award CHE-2107427. Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nano Coordinated Infrastructure Network (NNCI) under Award Number ECCS-2025124. Z.M. was supported by the NIH Chemical Biology Training Grant T32GM132029 and the NIH Functional Proteomics in Aging Training Grant 5T32AG029796-14. We also thank Kristen John for the generous donation of HEK-293 cells and valuable discussion.

Publisher Copyright:
© 2022 American Chemical Society


  • DNA tetrahedron
  • cell uptake
  • metallointercalator
  • serum stability
  • supramolecular self-assembly
  • Intercalating Agents/chemistry
  • Ruthenium/chemistry
  • DNA/chemistry
  • Base Pairing
  • Coordination Complexes
  • Organometallic Compounds/chemistry

PubMed: MeSH publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Journal Article
  • Research Support, N.I.H., Extramural


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