Adaptive Protein Corona Nanoassemblies Couple Cytokine Signaling with Endogenous Antigen Transport for Systemic...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Protein corona formation on nanoparticles is poorly controlled in biological settings.
• Programming nanoparticle interfaces for targeted biological functions remains a challenge.
• Developing strategies to harness protein corona for therapeutic benefit is crucial.

Purpose of the Study:

• To develop an adaptive protein corona nanoassembly strategy.
• To integrate cytokine signaling with endogenous antigen transport for cancer immunotherapy.
• To create nanoshuttles capable of dynamic protein recruitment and antigen capture in the tumor microenvironment.

Main Methods:

• Assembled coordination-engineered manganese nanoscaffolds with interleukin-12 (IL-12).
• Protected nanoscaffolds with an enzyme-responsive hyaluronic acid shell to form nanoshuttles (NSs).
• Investigated enzymatic activation, adaptive corona formation, antigen capture, and immune cell interactions in the tumor microenvironment (TME).

Main Results:

• Enzymatic activation exposed cationic manganese surfaces, promoting adaptive corona formation and tumor antigen capture.
• Resulting nanoassemblies trafficked to lymph nodes, facilitating dendritic cell cross-presentation and T-cell priming.
• Achieved potent systemic antitumor immunity with significantly reduced IL-12 doses.

Conclusions:

• Adaptive protein corona nanoassembly is a viable strategy for programming nano-bio interfaces.
• This approach effectively coordinates cytokine signaling and antigen transport for enhanced cancer immunotherapy.
• Demonstrated a novel method for creating functional protein coronas to improve therapeutic outcomes.