title: Multivalent presentation of MPL by porous silicon microparticles favors T helper 1 polarization enhancing the anti-tumor efficacy of doxorubicin nanoliposomes.
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-γ and TNF-α 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-1β 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.
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Ismail M
authors.initials: IM
authors.lastname: Meraz
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Hearnden
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Xuewu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin, Ireland.
authors.forename: Marie
authors.initials: M
authors.lastname: Yang
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin, Ireland.
authors.forename: Laura
authors.initials: L
authors.lastname: Williams
authors.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America; The University of Texas School of Medicine, Houston, Texas, United States of America.
authors.forename: David J
authors.initials: DJ
authors.lastname: Savage
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Gu
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Rhudy
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America.
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoi
authors.affiliation: Adjuvant Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin, Ireland; Advanced Materials and BioEngineering Research (AMBER), Centre for Research on Adaptive Nanostructures and Nanodevices (CRANN), Trinity College, Dublin, Ireland.
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
authors.affiliation: Nanomedicine, Houston Methodist Research Institute, Houston, Texas, United States of America; Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Rita E
authors.initials: RE
authors.lastname: Serda
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001692:Biological Transport; D001854:Bone Marrow Cells / Q000166:cytology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D008050:Lipid A / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology; D008081:Liposomes; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008863:Microspheres; D053758:Nanoparticles; D010316:Particle Size; D016062:Porosity; D012825:Silicon / Q000737:chemistry* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D016207:Cytokines; D008050:Lipid A; D008081:Liposomes; D004317:Doxorubicin; C048436:monophosphoryl lipid A; D012825:Silicon
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