A Programmed Streptavidin-Condensed Bifunctional Nucleic Acid Nanoplatform Breaking the Vicious Cycle for Traumatic...

Area of Science:

• Biomedical Engineering
• Neuroscience
• Nanotechnology

Background:

• Traumatic brain injury (TBI) therapy faces challenges due to the intertwined cycles of neuroinflammation and oxidative stress.
• Current treatments often fail to address both pathways concurrently, limiting efficacy.

Purpose of the Study:

• To develop a bifunctional nucleic acid nanoplatform (DZ-G4/H NPs) for simultaneous targeting of neuroinflammation and oxidative stress in TBI.
• To evaluate the therapeutic efficacy of this nanoplatform in a mouse model of TBI.

Main Methods:

• Programmed assembly of a bifunctional nucleic acid nanoplatform using rolling circle amplification (RCA).
• Integration of C1qa-cleaving DNAzymes and G-quadruplex/hemin (G4/H) complexes.
• Assessment of therapeutic effects in TBI mice, including alleviation of brain edema, restoration of cerebral blood flow (CBF), and functional recovery.

Main Results:

• The DZ-G4/H NPs demonstrated enhanced stability and drug-loading capacity.
• The nanoplatform effectively disrupted the inflammation-oxidative stress cycle, outperforming monotherapies.
• Significant improvements were observed in TBI mouse models, including reduced brain edema, improved CBF, enhanced motor and cognitive functions, and increased survival rates.

Conclusions:

• The developed nanoplatform offers a superior therapeutic strategy for TBI by concurrently targeting neuroinflammation and oxidative stress.
• This nanostrategy provides a versatile platform for developing multifunctional nucleic acid-based drugs for various therapeutic applications.