Journal
BIOMATERIALS
Volume 187, Issue -, Pages 105-116Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.09.029
Keywords
Nanoparticles; Magnetic enrichment; Artificial antigen-presenting cells; T cells; Immunotherapy; Size
Funding
- NIH Cancer Nanotechnology Training Center at the Johns Hopkins Institute for NanoBioTechnology
- National Science Foundation Graduate Research Fellowship [DGE-1232825]
- ARCS foundation
- National Science Foundation Graduate Research Fellowship
- TEDCO/Maryland Innovation Initiative
- Coulter Foundation (JPS)
- National Institutes of Health [P01-A1072677, R01-CA108835, R21-CA185819]
- NATIONAL CANCER INSTITUTE [R01CA108835, R21CA185819] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [P01AI072677] Funding Source: NIH RePORTER
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Magnetic particles can enrich desired cell populations to aid in understanding cell-type functions and mechanisms, diagnosis, and therapy. As cells are heterogeneous in ligand type, location, expression, and density, careful consideration of magnetic particle design for positive isolation is necessary. Antigen-specific immune cells have low frequencies, which has made studying, identifying, and utilizing these cells for therapy a challenge. Here we demonstrate the importance of magnetic particle design based on the biology of T cells. We create magnetic particles which recognize rare antigen-specific T cells and quantitatively investigate important particle properties including size, concentration, ligand density, and ligand choice in enriching these rare cells. We observe competing optima among particle parameters, with 300 nm particles functionalized with a high density of antigen-specific ligand achieving the highest enrichment and recovery of target cells. In enriching and then activating an endogenous response, 300 nm aAPCs generate nearly 65% antigen-specific T cells with at least 450-fold expansion from endogenous precursors and a 5-fold increase in numbers of antigen-specific cells after only seven days. This systematic study of particle properties in magnetic enrichment provides a case study for the engineering design principles of particles for the isolation of rare cells through biological ligands.
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