title: Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice.
abstract: Nanoparticles have been extensively developed for therapeutic and diagnostic applications. While the focus of nanoparticle trafficking in vivo has traditionally been on drug delivery and organ-level biodistribution and clearance, recent work in cancer biology and infectious disease suggests that targeting different cells within a given organ can substantially affect the quality of the immunological response. Here, we examine the cell-level biodistribution kinetics after administering ultrasmall Pluronic-stabilized poly(propylene sulfide) nanoparticles in the mouse. These nanoparticles depend on lymphatic drainage to reach the lymph nodes and blood, and then enter the spleen rather than the liver, where they interact with monocytes, macrophages and myeloid dendritic cells. They were more readily taken up into lymphatics after intradermal (i.d.) compared to intramuscular administration, leading to ∼50% increased bioavailability in blood. When administered i.d., their distribution favored antigen-presenting cells, with especially strong targeting to myeloid cells. In tumor-bearing mice, the monocytic and the polymorphonuclear myeloid-derived suppressor cell compartments were efficiently and preferentially targeted, rendering this nanoparticulate formulation potentially useful for reversing the highly suppressive activity of these cells in the tumor stroma.
authors.affiliation: Institute of Bioengineering, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Iraklis C
authors.initials: IC
authors.lastname: Kourtis
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hirosue
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Titta
authors.forename: Stephan
authors.initials: S
authors.lastname: Kontos
authors.forename: Toon
authors.initials: T
authors.lastname: Stegmann
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hubbell
authors.forename: Melody A
authors.initials: MA
authors.lastname: Swartz
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001682:Biological Availability; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005456:Fluorescent Dyes / Q000493:pharmacokinetics*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008223:Lymphoma / Q000097:blood / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D022423:Myeloid Cells / Q000378:metabolism* / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009368:Neoplasm Transplantation; D020442:Poloxamer / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D013440:Sulfides / Q000737:chemistry
chemical_list: D015703:Antigens, CD; D005456:Fluorescent Dyes; D011108:Polymers; D013440:Sulfides; C522256:poly(propylene sulfide); D020442:Poloxamer