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Using Well-Defined DNA Nanostructures To Study the Influence of DNA Clustering and Presentation on SNA Cellular
Yinglun Ma1,2, Jennifer Delgado1,2, Cuizheng Zhang1,2
1Department of Chemistry, Northwestern University, Evanston, Illinois 60208, United States.
Nano Letters
|May 5, 2026
Summary
Researchers optimized spherical nucleic acid (SNA) structures by altering DNA nanostructures. This modification significantly enhanced cellular uptake, demonstrating a 5-fold increase with a specific TX motif SNA, paving the way for improved biological applications.
Area of Science:
- Biotechnology
- Nanotechnology
- Molecular Biology
Background:
- Spherical nucleic acids (SNAs) are nucleic acid structures with significant biological functions.
- The impact of DNA nanostructure assembly on SNA properties, such as cellular uptake, is not fully understood.
Purpose of the Study:
- To investigate how well-defined DNA nanostructures on SNAs influence cellular uptake.
- To explore the relationship between DNA clustering, topology, and cellular internalization.
Main Methods:
- Synthesized three distinct DNA nanostructures assembled on preformed SNAs.
- Tested cellular uptake of these nanostructures across three cell lines (NIH-3T3, HaCaT, RAW 264.7).
- Analyzed the correlation between DNA clustering, Ca2+ binding, and uptake pathways.
Main Results:
- All tested nanostructured SNAs showed increased cellular uptake compared to conventional SNAs.
- One structure, the TX motif SNA, demonstrated a 5-fold increase in uptake after 4 hours.
- Higher DNA clustering and crossover correlated with enhanced Ca2+ binding and uptake via clathrin- and macropinocytosis-mediated pathways.
Conclusions:
- Structural modifications of the SNA shell can significantly enhance cellular uptake.
- Ca2+ binding within SNA structures plays a crucial role in facilitating cellular internalization.
- This research provides a strategy for optimizing SNA biological function through structural design.
