A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine

Veronica Liv Andersen, Mathias Vinther, Rajesh Kumar, Annika Ries, Jesper Wengel, Jesper Sejrup Nielsen, Jørgen Kjems*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual. Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold, and characterized its assembly, stability and functional properties in vitro and in vivo. We tested its flexibility towards multifunctionalization by conjugating various biomolecules to the four modules of the system. The pharmacokinetics, targeting capability and bioimaging properties of the structure were investigated in mice. The role of avidity in targeted liver cell internalization was investigated by flow cytometry, confocal microscopy and in vivo by fluorescent scanning of the blood and organs of the animals. Results: We have developed a nanoscaffold that rapidly and with high efficiency can self-assemble four chemically conjugated functionalities into a stable, in vivo-applicable system with complete control of stoichiometry and site specificity. The circulation time of the nanoscaffold could be tuned by functionalization with various numbers of polyethylene glycol polymers or with albumin-binding fatty acids. Highly effective hepatocyte-specific internalization was achieved with increasing valencies of tri-antennary galactosamine (triGalNAc) in vitro and in vivo. Conclusion: With its facile functionalization, stoichiometric control, small size and high serum- and thermostability, the nanoscaffold presented here constitutes a novel and flexible platform technology for theranostics.

Original languageEnglish
JournalTheranostics
Volume9
Issue number9
Pages (from-to)2662-2677
ISSN1838-7640
DOIs
Publication statusPublished - 2019

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Nucleic Acids
Medicine
Precision Medicine
Confocal Microscopy
Hepatocytes
Albumins
Flow Cytometry
Fatty Acids
Pharmacokinetics
Liver
Serum
Theranostic Nanomedicine
In Vitro Techniques

Cite this

Andersen, V. L., Vinther, M., Kumar, R., Ries, A., Wengel, J., Nielsen, J. S., & Kjems, J. (2019). A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine. Theranostics, 9(9), 2662-2677. https://doi.org/10.7150/thno.32060
Andersen, Veronica Liv ; Vinther, Mathias ; Kumar, Rajesh ; Ries, Annika ; Wengel, Jesper ; Nielsen, Jesper Sejrup ; Kjems, Jørgen. / A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine. In: Theranostics. 2019 ; Vol. 9, No. 9. pp. 2662-2677.
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abstract = "Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual. Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold, and characterized its assembly, stability and functional properties in vitro and in vivo. We tested its flexibility towards multifunctionalization by conjugating various biomolecules to the four modules of the system. The pharmacokinetics, targeting capability and bioimaging properties of the structure were investigated in mice. The role of avidity in targeted liver cell internalization was investigated by flow cytometry, confocal microscopy and in vivo by fluorescent scanning of the blood and organs of the animals. Results: We have developed a nanoscaffold that rapidly and with high efficiency can self-assemble four chemically conjugated functionalities into a stable, in vivo-applicable system with complete control of stoichiometry and site specificity. The circulation time of the nanoscaffold could be tuned by functionalization with various numbers of polyethylene glycol polymers or with albumin-binding fatty acids. Highly effective hepatocyte-specific internalization was achieved with increasing valencies of tri-antennary galactosamine (triGalNAc) in vitro and in vivo. Conclusion: With its facile functionalization, stoichiometric control, small size and high serum- and thermostability, the nanoscaffold presented here constitutes a novel and flexible platform technology for theranostics.",
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Andersen, VL, Vinther, M, Kumar, R, Ries, A, Wengel, J, Nielsen, JS & Kjems, J 2019, 'A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine', Theranostics, vol. 9, no. 9, pp. 2662-2677. https://doi.org/10.7150/thno.32060

A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine. / Andersen, Veronica Liv; Vinther, Mathias; Kumar, Rajesh; Ries, Annika; Wengel, Jesper; Nielsen, Jesper Sejrup; Kjems, Jørgen.

In: Theranostics, Vol. 9, No. 9, 2019, p. 2662-2677.

Research output: Contribution to journalJournal articleResearchpeer-review

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T1 - A self-assembled, modular nucleic acid-based nanoscaffold for multivalent theranostic medicine

AU - Andersen, Veronica Liv

AU - Vinther, Mathias

AU - Kumar, Rajesh

AU - Ries, Annika

AU - Wengel, Jesper

AU - Nielsen, Jesper Sejrup

AU - Kjems, Jørgen

PY - 2019

Y1 - 2019

N2 - Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual. Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold, and characterized its assembly, stability and functional properties in vitro and in vivo. We tested its flexibility towards multifunctionalization by conjugating various biomolecules to the four modules of the system. The pharmacokinetics, targeting capability and bioimaging properties of the structure were investigated in mice. The role of avidity in targeted liver cell internalization was investigated by flow cytometry, confocal microscopy and in vivo by fluorescent scanning of the blood and organs of the animals. Results: We have developed a nanoscaffold that rapidly and with high efficiency can self-assemble four chemically conjugated functionalities into a stable, in vivo-applicable system with complete control of stoichiometry and site specificity. The circulation time of the nanoscaffold could be tuned by functionalization with various numbers of polyethylene glycol polymers or with albumin-binding fatty acids. Highly effective hepatocyte-specific internalization was achieved with increasing valencies of tri-antennary galactosamine (triGalNAc) in vitro and in vivo. Conclusion: With its facile functionalization, stoichiometric control, small size and high serum- and thermostability, the nanoscaffold presented here constitutes a novel and flexible platform technology for theranostics.

AB - Rationale: Within the field of personalized medicine there is an increasing focus on designing flexible, multifunctional drug delivery systems that combine high efficacy with minimal side effects, by tailoring treatment to the individual. Methods: We synthesized a chemically stabilized ~4 nm nucleic acid nanoscaffold, and characterized its assembly, stability and functional properties in vitro and in vivo. We tested its flexibility towards multifunctionalization by conjugating various biomolecules to the four modules of the system. The pharmacokinetics, targeting capability and bioimaging properties of the structure were investigated in mice. The role of avidity in targeted liver cell internalization was investigated by flow cytometry, confocal microscopy and in vivo by fluorescent scanning of the blood and organs of the animals. Results: We have developed a nanoscaffold that rapidly and with high efficiency can self-assemble four chemically conjugated functionalities into a stable, in vivo-applicable system with complete control of stoichiometry and site specificity. The circulation time of the nanoscaffold could be tuned by functionalization with various numbers of polyethylene glycol polymers or with albumin-binding fatty acids. Highly effective hepatocyte-specific internalization was achieved with increasing valencies of tri-antennary galactosamine (triGalNAc) in vitro and in vivo. Conclusion: With its facile functionalization, stoichiometric control, small size and high serum- and thermostability, the nanoscaffold presented here constitutes a novel and flexible platform technology for theranostics.

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DO - 10.7150/thno.32060

M3 - Journal article

C2 - 31131060

VL - 9

SP - 2662

EP - 2677

JO - Theranostics

JF - Theranostics

SN - 1838-7640

IS - 9

ER -