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

doi:10.1021/acsnano.1c10084

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

Chemistry (Twin Cities)

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

Abstract

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 Tb^III 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 language	English (US)
Pages (from-to)	2928-2941
Number of pages	14
Journal	ACS nano
Volume	16
Issue number	2
DOIs	https://doi.org/10.1021/acsnano.1c10084
State	Published - 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

Keywords

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

Publisher link

10.1021/acsnano.1c10084

Find It

Find It at U of M Libraries

Cite this

@article{e60b7848bb9a4aa0890f1032c568c3f4,

title = "Metallointercalators-DNA Tetrahedron Supramolecular Self-Assemblies with Increased Serum Stability",

abstract = "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{\textquoteright}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.",

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

author = "Joaqui-Joaqui, {M. Andrey} and Zoe Maxwell and {Ramakrishnam Raju}, {Mandapati V.} and Min Jiang and Kriti Srivastava and Fangwei Shao and Arriaga, {Edgar A.} and Pierre, {Val{\'e}rie C.}",

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: {\textcopyright} 2022 American Chemical Society",

year = "2022",

month = feb,

day = "22",

doi = "10.1021/acsnano.1c10084",

language = "English (US)",

volume = "16",

pages = "2928--2941",

journal = "ACS nano",

issn = "1936-0851",

publisher = "American Chemical Society",

number = "2",

}

TY - JOUR

T1 - Metallointercalators-DNA Tetrahedron Supramolecular Self-Assemblies with Increased Serum Stability

AU - Joaqui-Joaqui, M. Andrey

AU - Maxwell, Zoe

AU - Ramakrishnam Raju, Mandapati V.

AU - Jiang, Min

AU - Srivastava, Kriti

AU - Shao, Fangwei

AU - Arriaga, Edgar A.

AU - Pierre, Valérie C.

N1 - 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

PY - 2022/2/22

Y1 - 2022/2/22

N2 - 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.

AB - 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.

KW - DNA tetrahedron

KW - cell uptake

KW - metallointercalator

KW - serum stability

KW - supramolecular self-assembly

KW - Intercalating Agents/chemistry

KW - Ruthenium/chemistry

KW - DNA/chemistry

KW - Base Pairing

KW - Coordination Complexes

KW - Organometallic Compounds/chemistry

UR - http://www.scopus.com/inward/record.url?scp=85125020039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85125020039&partnerID=8YFLogxK

U2 - 10.1021/acsnano.1c10084

DO - 10.1021/acsnano.1c10084

M3 - Article

C2 - 35133785

AN - SCOPUS:85125020039

SN - 1936-0851

VL - 16

SP - 2928

EP - 2941

JO - ACS nano

JF - ACS nano

IS - 2

ER -

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

Abstract

Bibliographical note

Keywords

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this