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Cell-Surface Binding of DNA Nanostructures for Enhanced Intracellular and Intranuclear Delivery
Weitao Wang1, Bhavya Chopra2, Vismaya Walawalkar1
1Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, United States.
ACS Applied Materials & Interfaces
|March 18, 2024
Summary
Cell-surface binding significantly enhances DNA nanostructure (DNs) delivery into cells and nuclei. This strategy, using cholesterol anchors or click chemistry, boosts uptake 2-8 fold within 30 minutes.
Area of Science:
- Biotechnology
- Nanomedicine
- Molecular Biology
Background:
- DNA nanostructures (DNs) offer tunable properties for biosensing, drug delivery, and therapeutics.
- Limited cellular uptake and nuclear delivery impede the efficacy of current DNA nanostructure applications.
Purpose of the Study:
- To investigate cell-surface binding as a strategy to enhance intracellular and intranuclear delivery of DNA nanostructures.
- To evaluate the impact of DN geometry and binding moiety characteristics on cellular uptake.
Main Methods:
- Targeting cell surfaces using cholesterol anchors or click chemistry to functionalize DNA nanostructures (nanospheres, nanorods, nanotiles).
- Quantifying cellular uptake and intranuclear delivery rates via flow cytometry and microscopy.
- Assessing DN structural stability in cell culture conditions and investigating endocytic pathways.
Main Results:
- Cell-surface binding increased cellular uptake of DNs by 2-8 fold within 30 minutes.
- Nanostructure geometry and binding moiety presentation significantly influenced uptake efficiency, with edge-decorated nanotiles showing superior performance.
- Cell-surface bound DNs utilized multiple endocytic pathways, similar to unmodified DNs, and demonstrated enhanced intranuclear delivery.
Conclusions:
- Cell-surface binding is a viable strategy to overcome low cellular uptake limitations of DNA nanostructures.
- This approach can significantly improve both cellular and nuclear delivery, expanding the potential applications of DNA nanostructures in medicine and biotechnology.
