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Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment

Show simple item record Popova, Taissia G. Teunis, Allison Magni, Ruben Luchini, Alessandra Espina, Virginia Liotta, Lance A. Popov, Serguei G. 2015-09-10T18:11:45Z 2015-09-10T18:11:45Z 2015-03-05
dc.identifier.citation Popova, T.G.; Teunis, A.; Magni, R.; Luchini, A.; Espina, V.; Liotta, L.A.; Popov, S.G. Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment. Nanomaterials 2015, 5, 298-320. en_US
dc.description.abstract 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.
dc.description.sponsorship This work was supported by the grant 5R21AI099851-2 from the National Institutes of Health, USA (S.G.P., V.E., and L.A.L.). Publication of this article was funded in part by the George Mason University Libraries Open Access Fund. en_US
dc.language.iso en_US en_US
dc.publisher Multidisciplinary Digital Publishing Institute en_US
dc.rights Attribution 3.0 United States *
dc.rights.uri *
dc.subject nanoparticles en_US
dc.subject chemokines en_US
dc.subject neutrophils en_US
dc.subject lymph node en_US
dc.title Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment en_US
dc.type Article en_US

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