Spherical Nucleic Acids with Tailored and Active Protein Coronae

Area of Science:

• Nanotechnology
• Bioconjugation
• Molecular Biology

Background:

• Spherical nucleic acids (SNAs) are nanomaterials with diverse biological applications.
• Protein coronae formation on SNAs in biological fluids can alter their function.
• Controlling protein interactions is crucial for effective SNA delivery.

Purpose of the Study:

• To design and synthesize SNAs with deliberately adsorbed functional proteins.
• To evaluate the impact of protein coatings on SNA stability, functionality, and biological interactions.
• To develop strategies for enhancing SNA targeting and biodistribution.

Main Methods:

• Synthesis of SNAs with adsorbed antibodies and serum albumin.
• Assessment of protease degradation resistance.
• Evaluation of hybridization capability with complementary oligonucleotides.
• Testing cellular selectivity in mixed cell populations.
• Quantification of macrophage uptake.
• Analysis of protein corona stability in human serum.

Main Results:

• Protein-adsorbed SNAs showed increased resistance to protease degradation while retaining hybridization function.
• SNAs with antibodies exhibited improved cellular selectivity in mixed populations.
• Serum albumin-coated SNAs demonstrated reduced macrophage uptake.
• Protein coronae remained stable on SNAs in human serum for over 12 hours.

Conclusions:

• Deliberately coating SNAs with functional proteins enhances their stability and targeting capabilities.
• Protein-SNA complexes offer a viable strategy for improving SNA biodistribution and selective delivery.
• This approach provides a new avenue for optimizing SNA performance in biological systems.