Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment
Taissia G. Popova,
Allison Teunis,
Ruben Magni,
Alessandra Luchini,
Virginia Espina,
Lance A. Liotta,
Serguei G. Popov
Affiliations
Taissia G. Popova
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Allison Teunis
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Ruben Magni
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Alessandra Luchini
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Virginia Espina
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Lance A. Liotta
Center for Applied Proteomics and Molecular Medicine, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Serguei G. Popov
National Center for Biodefense and Infectious Diseases, Department of Molecular Microbiology, School of Systems Biology, George Mason University, Manassas, VA 20110, USA
Chemokines (CKs) secreted by the host cells into surrounding tissue establish concentration gradients directing the migration of leukocytes. We propose an in vivo CK gradient remodeling approach based on sustained release of CKs by the crosslinked poly(N-isopropylacrylamide) hydrogel open meshwork nano-particles (NPs) containing internal crosslinked dye affinity baits for a reversible CK binding and release. The sustained release is based on a new principle of affinity off-rate tuning. The NPs with Cibacron Blue F3G-A and Reactive Blue-4 baits demonstrated a low-micromolar affinity binding to IL-8, MIP-2, and MCP-1 with a half-life of several hours at 37 °C. The capacity of NPs loaded with IL-8 and MIP-1α to increase neutrophil recruitment to lymph nodes (LNs) was tested in mice after footpad injection. Fluorescently-labeled NPs used as tracers indicated the delivery into the sub-capsular compartment of draining LNs. The animals administered the CK-loaded NPs demonstrated a widening of the sub-capsular space and a strong LN influx of leukocytes, while mice injected with control NPs without CKs or bolus doses of soluble CKs alone showed only a marginal neutrophil response. This technology provides a new means to therapeutically direct or restore immune cell traffic, and can also be employed for simultaneous therapy delivery.
