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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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DOE OSTI2023

Protein-Nanoparticle Interactions Govern the Interfacial Behavior of Polymeric Nanogels: Study of Protein Corona Formation at the Air/Water Interface

Biomedical applications of nanoparticles require a fundamental understanding of their interactions and behavior with biological interfaces. Protein corona formation can alter the morphology and properties of nanomaterials, and knowledge of the interfacial behavior of the complexes, using in situ analytical techniques, will impact the development of nanocarriers to maximize uptake and permeability at cellular interfaces. In this study we evaluate the interactions of acrylamide-based nanogels, with neutral, positive, and negative charges, with serum-abundant proteins albumin, fibrinogen, and immunoglobulin G. The formation of a protein corona complex between positively charged nanoparticles and albumin is characterized by dynamic light scattering, circular dichroism, and surface tensiometry; we use neutron reflectometry to resolve the complex structure at the air/water interface and demonstrate the effect of increased protein concentration on the interface. Surface tensiometry data suggest that the structure of the proteins can impact the interfacial properties of the complex formed. These results contribute to the understanding of the factors that influence the bio-nano interface, which will help to design nanomaterials with improved properties for applications in drug delivery.

Traldi, Federico (ORCID:0000000161251012)↗
DOE OSTI2021

A participant-derived xenograft model of HIV enables long-term evaluation of autologous immunotherapies

HIV-specific CD8+ T cells partially control viral replication and delay disease progression, but they rarely provide lasting protection, largely due to immune escape. Here, we show that engrafting mice with memory CD4+ T cells from HIV+ donors uniquely allows for the in vivo evaluation of autologous T cell responses while avoiding graft-versus-host disease and the need for human fetal tissues that limit other models. Treating HIV-infected mice with clinically relevant HIV-specific T cell products resulted in substantial reductions in viremia. In vivo activity was significantly enhanced when T cells were engineered with surface-conjugated nanogels carrying an IL-15 superagonist, but it was ultimately limited by the pervasive selection of a diverse array of escape mutations, recapitulating patterns seen in humans. By applying mathematical modeling, we show that the kinetics of the CD8+ T cell response have a profound impact on the emergence and persistence of escape mutations. This “participant-derived xenograft” model of HIV provides a powerful tool for studying HIV-specific immunological responses and facilitating the development of effective cell-based therapies.

60 APPLIED LIFE SCIENCES↗