Development of Pro-resolving and Pro-efferocytic Nanoparticles for Atherosclerosis Therapy

Area of Science:

• Cardiovascular Research
• Nanomedicine
• Immunology

Background:

• Atherosclerosis, a leading cause of cardiovascular disease, involves plaque buildup driven by inflammation and impaired efferocytosis.
• The CD47-SIRPα axis and overexpression of CD47 on plaques hinder macrophage clearance of apoptotic cells.
• Current therapies lower cardiovascular risk but don't address underlying disease mechanisms like inflammation and efferocytosis defects.

Purpose of the Study:

• To develop a combination nanotherapy for atherosclerosis targeting both inflammation and efferocytosis.
• To investigate the therapeutic potential of simultaneously enhancing efferocytosis and resolving inflammation.

Main Methods:

• Development of a dual-agent nanoparticle [(S + IL)-NPs] encapsulating an SHP-1 inhibitor (NSC 87877) and Interleukin-10 (IL-10).
• Evaluation of nanoparticle uptake by macrophages and intracellular delivery of agents.
• Assessment of the nanotherapy's effects on inflammatory markers and efferocytic activity via phosphoSTAT3 (pSTAT3) activation.

Main Results:

• The (S + IL)-NPs effectively encapsulated and delivered both the SHP-1 inhibitor and IL-10 into macrophages.
• Nanoparticle treatment significantly reduced pro-inflammatory markers and increased anti-inflammatory mediators.
• The nanotherapy demonstrated enhanced phagocytic activity, potentially through pSTAT3 pathway activation.

Conclusions:

• Combination nanotherapy with an SHP-1 inhibitor and IL-10 shows potential for treating atherosclerosis.
• This approach effectively enhances macrophage efferocytosis and promotes inflammation resolution.
• The nanomedicine strategy offers a promising avenue for managing atherosclerosis by modulating immune responses.