Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes

Ismailm Meraz, Claire H. Hearnden, Xuewu Liu, Marie Yang, Laura Williams, David J. Savage, Jianhua Gu, Jessica R. Rhudy, Kenji Yokoi, Ed C. Lavelle, Rita Serda

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Porous silicon (pSi) microparticles, in diverse sizes and shapes, can be functionalized to present pathogen-associated molecular patterns that activate dendritic cells. Intraperitoneal injection of MPL-adsorbed pSi microparticles, in contrast to free MPL, resulted in the induction of local inflammation, reflected in the recruitment of neutrophils, eosinophils and proinflammatory monocytes, and the depletion of resident macrophages and mast cells at the injection site. Injection of microparticle-bound MPL resulted in enhanced secretion of the T helper 1 associated cytokines IFN-c and TNF-a by peritoneal exudate and lymph node cells in response to secondary stimuli while decreasing the anti-inflammatory cytokine IL-10. MPL-pSi microparticles independently exhibited anti-tumor effects and enhanced tumor suppression by low dose doxorubicin nanoliposomes. Intravascular injection of the MPL-bound microparticles increased serum IL-1b levels, which was blocked by the IL-1 receptor antagonist Anakinra. The microparticles also potentiated tumor infiltration by dendritic cells, cytotoxic T lymphocytes, and F4/80+ macrophages, however, a specific reduction was observed in CD204+ macrophages.

Original languageEnglish (US)
Article numbere94703
JournalPLoS ONE
Volume9
Issue number4
DOIs
StatePublished - Apr 15 2014

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes'. Together they form a unique fingerprint.

Cite this