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Nanomaterials in the Context of Type 2 Immune Responses-Fears and Potentials.

ABSTRACT: The type 2 immune response is an adaptive immune program involved in defense against parasites, detoxification, and wound healing, but is predominantly known for its pathophysiological effects, manifesting as allergic disease. Engineered nanoparticles (NPs) are non-self entities that, to our knowledge, do not stimulate detrimental type 2 responses directly, but have the potential to modulate ongoing reactions in various ways, including the delivery of substances aiming at providing a therapeutic benefit. We review, here, the state of knowledge concerning the interaction of NPs with type 2 immune responses and highlight their potential as a multifunctional platform for therapeutic intervention.

SUBMITTER: Himly M

PROVIDER: S-EPMC5403887 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Nanomaterials in the Context of Type 2 Immune Responses-Fears and Potentials.

Himly Martin M Mills-Goodlet Robert R Geppert Mark M Duschl Albert A

Frontiers in immunology 20170425

The type 2 immune response is an adaptive immune program involved in defense against parasites, detoxification, and wound healing, but is predominantly known for its pathophysiological effects, manifesting as allergic disease. Engineered nanoparticles (NPs) are non-self entities that, to our knowledge, do not stimulate detrimental type 2 responses directly, but have the potential to modulate ongoing reactions in various ways, including the delivery of substances aiming at providing a therapeutic ...[more]

PMID: 28487697

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Project description:Traditional tissue regeneration approaches to activate cell behaviors on biomaterials rely on the use of extracellular-matrix-based or soluble growth-factor cues. In this article, a novel approach is highlighted to dynamically steer cellular phenomena such as cell motility based on nanoscale substratum features of biological ligands. Albumin-derived nanocarriers (ANCs) with variable nanoscale-size features are functionalized with fibronectin III9-10 matrix ligands, and their effects on primary human keratinocyte activation are investigated. The presentation of fibronectin fragments from ANCs significantly enhances cell migration as compared to free ligands at equivalent concentrations. Notably, cell migration is influenced by the size of the underlying ANCs even for variably sized ANCs covered in comparable levels of fibronectin fragment. For equivalent ligand concentrations, cell migration on the smaller-sized ANCs (30 and 50 nm) is significantly enhanced as compared to that on larger-sized ANCs (75 and 100 nm). In contrast, the enhancement of cell migration on nanocarriers is abolished by the use of immobilized, biofunctionalized ANCs, indicating that "dynamic" nanocarrier internalization events underlie the role of nanocarrier geometry on the differential regulation of cell migration kinetics. Uptake studies using fluorescent ANCs indicate that larger-sized ANCs cause delayed endocytic kinetics and hence could present barriers for internalization during the cell adhesion and motility processes. Motile cells exhibit diminished migration upon exposure to clathrin inhibitors, but not caveolin inhibitors, suggesting the role of clathrin-mediated endocytosis in facilitating cell migratory responsiveness to the nanocarriers. Overall, a monotonic relationship is found between the nanocarrier cytointernalization rate and the cell migration rate, suggesting the possibility of designing biointerfacial features for the dynamic control of cell migration. Thus, the functionalization of a mobile nanocarrier by a biorelevant ligand can be used to sensitize cellular motility activation to the adhesion ligands, and such nanocarrier interfaces can dynamically attune cell migration kinetics by modulating the uptake of the ligand-nanocarrier complex via nanocarrier size.

Dataset Information

Nanomaterials in the Context of Type 2 Immune Responses-Fears and Potentials.

Publications

Nanomaterials in the Context of Type 2 Immune Responses-Fears and Potentials.

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