Spherical Nucleic Acids with Sheddable PEG Layers

• Chad Mirkin* (Northwestern University, Weinberg College of Arts and Sciences, Department of Chemistry, Director of the International Institute for Nanotechnology (IIN))
• Brian Meckes
• Wuliang Zhang

SHORT DESCRIPTION

For oncology applications, this invention offers spherical nucleic acids with an enzyme-cleavable PEG layer that combines prolonged circulation with enhanced tumor cell uptake.

BACKGROUND

Conventional nanomaterials struggle to balance stability during circulation with effective delivery into tumor cells. The need exists for a robust technology that overcomes these challenges without undesired immunogenicity.

ABSTRACT

This invention presents a spherical nucleic acid (SNA) platform with a sheddable PEG layer attached via an enzyme-cleavable peptide linker. The design protects the nucleic acids in blood following systemic administration while allowing targeted PEG removal by tumor-overexpressed matrix metalloproteinases (MMPs). Laboratory studies confirm that these SNAs possessed prolonged blood circulation with minimal immune response and enhanced cellular uptake in tumor microenvironments relative to non-sheddable counterparts. The approach provides a promising route for targeted therapeutic delivery and gene regulation in oncology.


APPLICATIONS

• Targeted therapeutic delivery for precise tumor treatment.
• Gene regulation
• Diagnostic imaging

• Enhances circulation stability
• Improves tumor selectivity
• Provides a versatile platform.

• Chad Mirkin et al, Tumor-Associated Enzyme-Activatable Spherical Nucleic Acids, ACS Nano, 2022 Jul 18;16(7):10931–10942

IP STATUS

US Patent Pending.