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Models and Methods to Evaluate Transport of Drug Delivery Systems Across Cellular Barriers
Published on: October 17, 2013
Composition-Programmed Transport Inversion in Spherical Nucleic Acids across Distinct Epithelial Barriers
Xiuying Sun1, Rui Xu2, Huiwei Zhang3
1School of Materials Science and Engineering, Tianjin University, Tianjin 300350, China.
Journal of the American Chemical Society
|July 27, 2026
Summary
Surface composition of barrier-adaptive spherical nucleic acids (BASNAs) can reverse transport preference across biological barriers. Modulating poly(carboxybetaine) and antisense oligonucleotide ratios controls BASNA interactions for targeted delivery.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Molecular Biology
Background:
- Spherical nucleic acids (SNAs) offer versatile platforms for nucleic acid delivery.
- Controlling nanoparticle interactions with biological barriers is crucial for effective drug delivery.
- Understanding how surface properties influence transport across different epithelial layers remains a challenge.
Purpose of the Study:
- To investigate if surface composition alone can alter transport preference of nanostructures across distinct biological barriers.
- To develop barrier-adaptive spherical nucleic acids (BASNAs) with tunable surface properties.
- To explore the potential of BASNAs for targeted delivery and therapeutic applications.
Main Methods:
- Synthesized fully organic, reducible polymeric SNAs (BASNAs) with covalently cografted antisense oligonucleotides (ASO) and poly(carboxybetaine) (pCB) chains.
- Systematically modulated the pCB-to-ASO ratio to vary the surface composition of BASNAs.
- Evaluated BASNA transport across mucus and stratum corneum barriers.
- Assessed sequence-specific hybridization, duplex stability, nuclease resistance, and intracellular delivery efficiency.
- Tested in vivo efficacy in prophylactic atopic dermatitis and therapeutic allergic rhinitis models.
Main Results:
- Varying the pCB-to-ASO ratio inverted BASNA transport preference between mucus and stratum corneum barriers.
- Higher pCB content facilitated mucus diffusion via a hydrated interface, while lower pCB content promoted stratum corneum transport.
- BASNAs maintained sequence-specific activity, enhanced duplex stability, resisted nucleases, and improved intracellular delivery.
- In vivo, barrier-matched BASNAs achieved FcεRIβ silencing, preventing and suppressing inflammatory symptoms in atopic dermatitis and allergic rhinitis models.
Conclusions:
- Interfacial surface composition is a critical parameter for controlling nanostructure transport across biological barriers.
- BASNAs provide a tunable platform for overcoming biological barriers by adjusting surface chemistry.
- Surface composition engineering of nanostructures can reverse barrier preference within a fixed nanostructure topology, enabling targeted delivery and therapeutic intervention.
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