Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects

Yusuke Kawamoto; You Wu; Soyoung Park; Kumi Hidaka; Hiroshi Sugiyama; Yuki Takahashi; Yoshinobu Takakura

doi:10.1039/D4CC00578C

Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects†

Yusuke Kawamoto,

*^a You Wu,^a Soyoung Park,

^b Kumi Hidaka,^c Hiroshi Sugiyama,

^cd Yuki Takahashi

^a and Yoshinobu Takakura*^a

Author affiliations

* Corresponding authors

^a Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachicho, Sakyo-ku, Kyoto 606-8501, Japan
E-mail: y.kawamoto@pharm.kyoto-u.ac.jp, takakura@pharm.kyoto-u.ac.jp

^b Immunology Frontier Research Center, Osaka University, Yamadaoka, Suita, Osaka 565-0871, Japan

^c Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan

^d Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Yoshida-ushinomiyacho, Sakyo-ku, Kyoto 606-8501, Japan

Abstract

Dendritic DNA molecules, referred to as DNA dendrons, consist of multiple covalently linked strands and are expected to improve the cellular uptake and potency of therapeutic oligonucleotides because of their multivalency. In this study, we developed an efficient synthetic method for producing DNA dendrons using strain-promoted azide–alkyne cycloaddition. Integration of the antitumor aptamer AS1411 into DNA dendrons enhanced cellular uptake and antiproliferative activity in cancer cells. These findings demonstrate that the incorporation of multivalent aptamers into DNA dendrons can effectively boost their therapeutic effects.

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DOI: https://doi.org/10.1039/D4CC00578C
Article type: Communication
Submitted: 04 Feb 2024
Accepted: 06 May 2024
First published: 13 May 2024
This article is Open Access

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Chem. Commun., 2024, Advance Article

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Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects

Y. Kawamoto, Y. Wu, S. Park, K. Hidaka, H. Sugiyama, Y. Takahashi and Y. Takakura, Chem. Commun., 2024, Advance Article , DOI: 10.1039/D4CC00578C

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Chemical Communications

Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects†

Abstract

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Multivalent dendritic DNA aptamer molecules for the enhancement of therapeutic effects

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