Dataset Information

Proteomic analysis of antigen-capturing nanoparticles

ABSTRACT: Immunotherapy holds tremendous promise for improving cancer treatment. Administering radiotherapy with immunotherapy has been shown to improve immune responses and can elicit an “abscopal effect”. Unfortunately, response rates for this strategy remain low. Herein, we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NPs formulations and by using a proteomic approach, we demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent upon NP surface properties.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Laura Herring

LAB HEAD: Andrew Z. Wang

PROVIDER: PXD006049 | Pride | 2018-10-26

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2014_08_13C_P307_Wang_S2.msf	Msf
	2014_08_13C_P307_Wang_S2.raw	Raw
	2014_08_13E_P307_Wang_S3.msf	Msf
	2014_08_13E_P307_Wang_S3.raw	Raw
	2014_08_13G_P307_Wang_S4.msf	Msf

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Publications

Antigen-capturing nanoparticles improve the abscopal effect and cancer immunotherapy.

Min Yuanzeng Y Roche Kyle C KC Tian Shaomin S Eblan Michael J MJ McKinnon Karen P KP Caster Joseph M JM Chai Shengjie S Herring Laura E LE Zhang Longzhen L Zhang Tian T DeSimone Joseph M JM Tepper Joel E JE Vincent Benjamin G BG Serody Jonathan S JS Wang Andrew Z AZ

Nature nanotechnology 20170626 9

Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation i ...[more]

PMID: 28650437

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Project description:Poly-ethylene-glycol (PEG)-based nanoparticles (NPs) - including cylindrical micelles (CNPs), spherical micelles (SNPs), and PEGylated liposomes (PLs) - are hypothesized to be cleared in vivo by opsonization followed by liver macrophage phagocytosis. This hypothesis has been used to explain the rapid and significant localization of NPs to the liver after administration into the mammalian vasculature. Here, we show that the opsonization-phagocytosis nexus is not the major factor driving PEG-NP – macrophage interactions. First, mouse and human blood proteins had insignificant affinity for PEG-NPs. Second, PEG-NPs bound macrophages in the absence of serum proteins. Third, lipoproteins blocked PEG-NP binding to macrophages. Because of these findings, we tested the postulate that PEG-NPs bind (apo)lipoprotein receptors. Indeed, PEG-NPs triggered an in vitro macrophage transcription program that was similar to that triggered by lipoproteins and different from that triggered by lipopolysaccharide (LPS) and group A Streptococcus. Unlike LPS and pathogens, PLs did not increase transcripts involved in phagocytosis or inflammation. High-density lipoprotein (HDL) and SNPs triggered remarkably similar mouse bone-marrow-derived macrophage transcription programs. Unlike opsonized pathogens, CNPs, SNPs, and PLs lowered macrophage autophagosome levels and either reduced or did not increase the secretion of key macrophage pro-inflammatory cytokines and chemokines. Thus, the sequential opsonization and phagocytosis process is likely a minor aspect of PEG-NP – macrophage interactions. Instead, PEG-NP interactions with (apo)lipoprotein and scavenger receptors appear to be a strong driving force for PEG-NP – macrophage binding, entry, and downstream effects. We hypothesize that the high presence of these receptors on liver macrophages and on liver sinusoidal endothelial cells is the reason PEG-NPs localize rapidly and strongly to the liver. To investigate the response of macrophages to nanoparticles, we incubated PEGylated liposomes (PLs), spherical nanoparticles (SNPs), high-density lipoproteins (HDL), low-density lipoproteins (LDL), Group A Streptococcus pathogens (JRS4), and lipopolysaccharide (LPS) with RAW264.7 and primary bone-marrow derived mouse macrophages