Programming Aggregate States of DNA Nanorods with Sub-10 nm Hydrophobic Patterns for Tunable Cell Entry

Shuting Cao; Lixuan Lin; Yan Zhao; Linjie Guo; Ying Zhu; Lihua Wang; Jiang Li

doi:10.1021/jacsau.3c00097

Programming Aggregate States of DNA Nanorods with Sub-10 nm Hydrophobic Patterns for Tunable Cell Entry

JACS Au. 2023 Mar 20;3(4):1004-1009. doi: 10.1021/jacsau.3c00097. eCollection 2023 Apr 24.

Authors

Shuting Cao^{1

2

3}, Lixuan Lin^{1

2

3}, Yan Zhao⁴, Linjie Guo^{3

5}, Ying Zhu^{1

2

3

5}, Lihua Wang^{1

2

3

5}, Jiang Li^{1

2

3

5}

Affiliations

¹ Division of Physical Biology, CAS Key Laboratory of Interfacial Physics and Technology, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China.
² University of Chinese Academy of Sciences, Beijing 100049, China.
³ The Interdisciplinary Research Center, Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, China.
⁴ Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen 518132, China.
⁵ Institute of Materials Biology, Shanghai University, Shanghai 200444, China.

Abstract

The intracellular application of DNA nanodevices is challenged by their inadequate cellular entry efficiency, which may be addressed by the development of amphiphilic DNA nanostructures. However, the impact of the spatial distribution of hydrophobicity in cell entry has not been fully explored. Here, we program a spectrum of amphiphilic DNA nanostructures displaying diverse sub-10 nm patterns of cholesterol, which result in distinct aggregate states in the aqueous solution and thus varied cell entry efficiencies. We find that the hydrophobic patterns can lead to discrete aggregate states, from monomers to low-number oligomers (n = 1-6). We demonstrate that the monomers or oligomers with moderate hydrophobic density are preferred for cell entry, with up to ∼174-fold improvement relative to unmodified ones. Our study provides a new clue for the rational design of amphiphilic DNA nanostructures for intracellular applications.