Peripherally administered nanoparticles target monocytic myeloid cells, secondary lymphoid organs and tumors in mice

• Published in: PloS one Vol. 8; no. 4; p. e61646
• Main Authors: Kourtis, Iraklis C, Hirosue, Sachiko, de Titta, Alexandre, Kontos, Stephan, Stegmann, Toon, Hubbell, Jeffrey A, Swartz, Melody A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.04.2013; Public Library of Science (PLoS)
• Subjects: Animals; Antigen-presenting cells; Antigens, CD; B cells; Bioavailability; Bioengineering; Biological Availability; Biology; Blood; Cancer; Compartments; Dendritic cells; Dendritic Cells - metabolism; Dendritic Cells - pathology; Diagnostic software; Diagnostic systems; Drug delivery; Drug delivery systems; Evaluation; Female; Fluorescent Dyes - pharmacokinetics; Health aspects; Immunoglobulins; Immunology; Infectious diseases; Injections, Intradermal; Injections, Intramuscular; Kinetics; Ligands; Liver; Lymph nodes; Lymph Nodes - metabolism; Lymph Nodes - pathology; Lymphatic drainage; Lymphoma - blood; Lymphoma - pathology; Macrophages; Materials Science; Mice; Mice, Inbred C57BL; Monocytes; Monocytes - metabolism; Monocytes - pathology; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - pathology; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Neoplasm Transplantation; Organs; Poloxamer - chemistry; Polymers - chemistry; Propylene; Reaction kinetics; Reversing; Rodents; Spleen; Spleen - metabolism; Spleen - pathology; Stroma; Sulfide; Sulfides - chemistry; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0061646

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.