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<p>T cells are critically important to many diseases but are traditionally difficult to transfect. We hypothesise that the delivery of therapeutic cargo to T cells can be improved by targeting nanoparticles to surface receptors that undergo rapid receptor-mediated endocytosis. Using an internalisation assay that labelled intracellular and surface proteins with different fluorophores, we find that CD2 and CD7 exhibit significantly higher internalisation than other T cell receptors, such as CD3 or CD4. Targeting CD2 and CD7 improves nanoparticle internalisation by non-stimulated, primary CD4<sup>+</sup> T cells and enhances the specificity of association to CD4<sup>+</sup> T cells. Similarly, functionalising mRNA-lipid nanoparticles with antibodies targeting CD2 or CD7 enhances mRNA delivery to CD4<sup>+</sup> T cells in vitro. Importantly, targeting CD2 or CD7 enables efficient lipid nanoparticle-mediated delivery of mRNA to T cells in blood and lymphoid tissue in vivo, demonstrating that targeting T cell receptor endocytosis can enhance nanoparticle-mediated drug delivery to T cells.</p>

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Targeting rapidly cycling receptors CD2 and CD7 increases nanoparticle delivery to primary CD4+ T cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月1日

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  • Paula M. Cevaal,
  • Abdalla Ali,
  • Marcel Doerflinger,
  • Christina Cortez-Jugo,
  • Abigail Tan,
  • Haiyin Liu,
  • Moore Z. Chen,
  • Le Wang,
  • Merle Dayton,
  • Liana Mackiewicz,
  • Stanislav Kan,
  • Matthew Faria,
  • Celine Gubser,
  • René P. M. Lafleur,
  • Robert De Rose,
  • Angus P. R. Johnston,
  • Frank Caruso,
  • Michael Roche,
  • Jori Symons,
  • Sharon R. Lewin

摘要

T cells are critically important to many diseases but are traditionally difficult to transfect. We hypothesise that the delivery of therapeutic cargo to T cells can be improved by targeting nanoparticles to surface receptors that undergo rapid receptor-mediated endocytosis. Using an internalisation assay that labelled intracellular and surface proteins with different fluorophores, we find that CD2 and CD7 exhibit significantly higher internalisation than other T cell receptors, such as CD3 or CD4. Targeting CD2 and CD7 improves nanoparticle internalisation by non-stimulated, primary CD4+ T cells and enhances the specificity of association to CD4+ T cells. Similarly, functionalising mRNA-lipid nanoparticles with antibodies targeting CD2 or CD7 enhances mRNA delivery to CD4+ T cells in vitro. Importantly, targeting CD2 or CD7 enables efficient lipid nanoparticle-mediated delivery of mRNA to T cells in blood and lymphoid tissue in vivo, demonstrating that targeting T cell receptor endocytosis can enhance nanoparticle-mediated drug delivery to T cells.