A DNA Origami Nanodevice Programs CD20 Spatial Organization for Selective Apoptosis of Malignant B Cells in Lymphoma Therapy

Abstract

Triggering CD20 clustering to induce B cell apoptosis is considered a promising therapeutic strategy for dysregulated, B cell-driven diseases, yet current methods lack the spatial precision to organize CD20 into defined clusters and fail to discriminate malignant from normal B cells. Here, we describe an intelligent DNA origami nanodevice that integrates an optimized anti-CD20 antibody array with a conformational switch to selectively induce CD20 clustering and apoptosis in B-cell lymphoma. Benefiting from the nanometric precision of DNA origami, we found that arranging anti-CD20 antibodies into a pentavalent array with approximately 10 nm spacing most effectively drives CD20 clustering and downstream apoptosis. Under resting conditions, the nanodevice stays in a closed, tubular shape that conceals the antibody array inside and therefore remains harmless to normal B cells. Upon encountering c-Met expressed on lymphoma B cells, the device unrolls into a planar sheet and exposes the antibody array, triggering potent apoptotic signaling specifically in these malignant cells. In a Raji xenograft mouse model, intravenously injected nanodevices specifically unrolled at the tumor site, inhibited tumor growth by more than 70%, and produced no significant systemic toxicity. By coupling programmable ligand nanopatterning with a shape-changing switch, this DNA origami platform offers a generalizable strategy for receptor-mediated disease therapy.