Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice

Iraklis C. Kourtis, Sachiko Hirosue, Alexandre de Titta, Stephan Kontos, Toon Stegmann, Jeffrey A. Hubbell, Melody A. Swartz

Research output: Contribution to journalArticle

76 Citations (Scopus)

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.

Original languageEnglish
Article numbere61646
JournalPLoS One
Volume8
Issue number4
DOIs
StatePublished - Apr 23 2013
Externally publishedYes

Fingerprint

nanoparticles
Myeloid Cells
Nanoparticles
Tumors
neoplasms
mice
Neoplasms
Blood
Bearings (structural)
cells
propylene
suppressor cells
Poloxamer
antigen-presenting cells
Macrophages
blood
rendering
Antigen-Presenting Cells
dendritic cells
intramuscular injection

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kourtis, I. C., Hirosue, S., de Titta, A., Kontos, S., Stegmann, T., Hubbell, J. A., & Swartz, M. A. (2013). Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice. PLoS One, 8(4), [e61646]. https://doi.org/10.1371/journal.pone.0061646

Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice. / Kourtis, Iraklis C.; Hirosue, Sachiko; de Titta, Alexandre; Kontos, Stephan; Stegmann, Toon; Hubbell, Jeffrey A.; Swartz, Melody A.

In: PLoS One, Vol. 8, No. 4, e61646, 23.04.2013.

Research output: Contribution to journalArticle

Kourtis, IC, Hirosue, S, de Titta, A, Kontos, S, Stegmann, T, Hubbell, JA & Swartz, MA 2013, 'Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice', PLoS One, vol. 8, no. 4, e61646. https://doi.org/10.1371/journal.pone.0061646
Kourtis, Iraklis C. ; Hirosue, Sachiko ; de Titta, Alexandre ; Kontos, Stephan ; Stegmann, Toon ; Hubbell, Jeffrey A. ; Swartz, Melody A. / Peripherally Administered Nanoparticles Target Monocytic Myeloid Cells, Secondary Lymphoid Organs and Tumors in Mice. In: PLoS One. 2013 ; Vol. 8, No. 4.
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