Chemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment

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dc.contributor.authorPopova, Taissia G.
dc.contributor.authorTeunis, Allison
dc.contributor.authorMagni, Ruben
dc.contributor.authorLuchini, Alessandra
dc.contributor.authorEspina, Virginia
dc.contributor.authorLiotta, Lance A.
dc.contributor.authorPopov, Serguei G.
dc.date.accessioned2015-09-10T18:11:45Z
dc.date.available2015-09-10T18:11:45Z
dc.date.issued2015-03-05
dc.description.abstractChemokines (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.sponsorshipThis 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.
dc.identifier.citationPopova, 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.
dc.identifier.doihttp://dx.doi.org/10.3390/nano5010298
dc.identifier.urihttps://hdl.handle.net/1920/9832
dc.language.isoen_US
dc.publisherMultidisciplinary Digital Publishing Institute
dc.rightsAttribution 3.0 United States
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subjectNanoparticles
dc.subjectChemokines
dc.subjectNeutrophils
dc.subjectLymph node
dc.titleChemokine-Releasing Nanoparticles for Manipulation of the Lymph Node Microenvironment
dc.typeArticle

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