PLGA Spherical Nucleic Acids

Area of Science:

• Nanotechnology
• Polymer Science
• Bioconjugation

Background:

• Spherical nucleic acids (SNAs) are promising nanostructures for biomedical applications.
• Existing SNA platforms often utilize gold nanoparticles, limiting drug encapsulation and release tunability.
• There is a need for versatile SNA platforms that can incorporate therapeutic payloads and offer controlled release.

Purpose of the Study:

• To develop a novel class of polymer-based spherical nucleic acid (SNA) conjugates.
• To investigate the drug encapsulation and release properties of these new poly(lactic-co-glycolic acid) (PLGA)-SNA constructs.
• To evaluate the cellular uptake and biological activity of PLGA-SNAs.

Main Methods:

• Synthesis of poly(lactic-co-glycolic acid) (PLGA) nanoparticle cores.
• Conjugation of nucleic acid shells to PLGA nanoparticle cores to form PLGA-SNAs.
• Encapsulation of a hydrophobic model drug (coumarin 6) within the PLGA core.
• Assessment of drug release kinetics as a function of polymer composition.
• Evaluation of the stability and half-life of PLGA-SNAs in biological media (fetal bovine serum).
• Cellular uptake studies using Raw-Blue cells.
• Activation of Toll-like receptor 9 (TLR9) by PLGA-SNAs.

Main Results:

• A new class of PLGA-SNA conjugates was successfully synthesized.
• PLGA-SNAs demonstrated a half-life exceeding 2 hours in fetal bovine serum.
• Hydrophobic drugs could be encapsulated and released in a tunable manner dependent on PLGA composition.
• Nucleic acid shell dissociation remained constant irrespective of the core composition.
• PLGA-SNAs exhibited efficient cellular uptake into Raw-Blue cells.
• Sequence- and dose-dependent activation of Toll-like receptor 9 was observed.

Conclusions:

• PLGA-SNAs represent a novel nanoconstruct with tunable drug release capabilities.
• The platform allows for controlled release of encapsulated cargos within the SNA framework.
• PLGA-SNAs can engage with cellular pathways, such as TLR9 activation.
• This versatile nanoplatform holds potential for developing advanced combination therapeutics.