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

Cevaal, PM; Ali, A; Doerflinger, M; Cortez-Jugo, C; Tan, A; Liu, H; Chen, MZ; Wang, L; Dayton, M; Mackiewicz, L; Kan, S; Faria, M; Gubser, C; Lafleur, RPM; De Rose, R; Johnston, APR; Caruso, F; Roche, M; Symons, J; Lewin, SR

Author(s): Cevaal, PM; Ali, A; Doerflinger, M; Cortez-Jugo, C; Tan, A; Liu, H; Chen, MZ; Wang, L; Dayton, M; Mackiewicz, L; Kan, S; Faria, M; Gubser, C; Lafleur, RPM; De Rose, R; Johnston, APR; Caruso, F; Roche, M; Symons, J; Lewin, SR;
Details: Publication Year 2026-07-01,Volume 17,Issue #1,Page 8204
Journal Title: Nature Communications
Abstract: 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.
Publisher: Springer Nature
Keywords: *CD4-Positive T-Lymphocytes/metabolism; Animals; *Nanoparticles/chemistry; Endocytosis; *CD2 Antigens/metabolism/immunology; *Antigens, CD7/metabolism/immunology; RNA, Messenger/metabolism; Mice; Humans; Drug Delivery Systems; Mice, Inbred C57BL
Research Division(s): Infection and Global Health
PubMed ID: 42386746
Publisher's Version: https://doi.org/10.1038/s41467-026-74981-2
Open Access at Publisher's Site: https://doi.org/10.1038/s41467-026-74981-2
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2026-07-09 08:59:07

Last Modified: 2026-08-14 11:30:41