Graphene oxide activates B cells with upregulation of granzyme B expression: Evidence at the single-cell level for its immune-modulatory properties and anticancer activity

Marco Orecchioni, Laura Fusco, Raghvendra Mall, Valentina Bordoni, Claudia Fuoco, Darawan Rinchai, Shi Guo, Raquel Sainz, Martina Zoccheddu, Cansu Gurcan, Acelya Yilmazer, Barbara Zavan, Cécilia Ménard-Moyon, Alberto Bianco, Wouter Hendrickx, Davide Bedognetti, Lucia Gemma Delogu

Research output: Contribution to journalArticlepeer-review

Abstract

We recently found by single-cell mass cytometry that ex vivo human B cells internalize graphene oxide (GO). The functional impact of such uptake on B cells remains unexplored. Here, we disclosed the effects of GO and amino-functionalized GO (GONH2) interacting with human B cells in vitro and ex vivo at the protein and gene expression levels. Moreover, our study considered three different subpopulations of B cells and their functionality in terms of: (i) cytokine production, (ii) activation markers, (iii) killing activity towards cancer cells. Single-cell mass cytometry screening revealed the higher impact of GO on cell viability towards naïve, memory, and plasma B cell subsets. Different cytokines such as granzyme B (GrB) and activation markers, like CD69, CD80, CD138, and CD38, were differently regulated by GONH2 compared to GO, supporting possible diverse B cell activation paths. Moreover, co-culture experiments also suggest the functional ability of both GOs to activate B cells and therefore enhance the toxicity towards HeLa cancer cell line. Complete transcriptomic analysis on a B cell line highlighted the distinctive GO and GONH2 elicited responses, inducing pathways such as B cell receptor and CD40 signaling pathways, key players for GrB secretion. B cells were regularly left behind the scenes in graphene biological studies; our results may open new horizons in the development of GO-based immune-modulatory strategies having B cell as main actors.

Original languageEnglish (US)
Pages (from-to)333-349
Number of pages17
JournalNanoscale
Volume14
Issue number2
DOIs
StatePublished - 2022

ASJC Scopus subject areas

  • Materials Science(all)

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