Unraveling Nanomedicine Complexities: Anti-Inflammatory Immunomodulation and Biomolecular Corona Immunogenicity Dissected

Sepsis is a life-threatening condition of complex pathophysiological origin that develops due to an uncontrolled host immune response to an infection. In 2017, an estimated 48.9 million incident cases of sepsis were recorded worldwide, and sepsis-related deaths represented one-fifth (20%) of all global deaths. Despite the severity of this condition, there are currently no FDA-approved treatment options that improve patient survival, even though over 100 therapeutic clinical trials have been conducted. To address this issue, we are exploring the use of nanoparticles to modulate the responses of innate and adaptive immune cells with the aim to restore immune homeostasis and improve outcomes in lethal severe inflammation and polymicrobial sepsis murine models. In this presentation, I will highlight various strategies utilized by our group including scalable microfluidic nanoparticle formulation and purification methods, the impact of formulation parameters on anti-inflammatory effects, small molecule drug delivery, and the multimodal in vivo mechanisms leveraged by nanoparticles to improve survival outcomes. Finally, I will highlight our collaborative efforts utilizing integrated multiOmics approaches to characterize the impacts of the biomolecular corona and its toxicological implications as a function of inflammatory disease state. Overall, this comprehensive discussion of anti-inflammatory nanoparticle technologies and their cellular and molecular mechanisms will facilitate a thought-provoking discussion of nanoimmunotherapies and their key considerations for use as therapeutic agents.