Electronic bra for noninvasive transdermal gene delivery in neoadjuvant therapy of triple-negative breast cancer

Safe and non-invasive physical delivery tools for nucleic acids provide new therapeutic options for diseases lacking targets, such as triple-negative breast cancer (TNBC). However, existing electroporation devices rely on high voltages and rigid electrode materials. Here we propose an electronic bra (termed NEO-BRA) capable of noninvasive electroporation for transdermal gene therapy as a neoadjuvant therapy for TNBC. The NEO-BRA integrates intrinsically flexible substrates and liquid metal-polymer conductors, enabling conformal contact with target tissue. High-density, 3D structured conductors resulted in electrotransfection of nucleic acids at the lowest voltage (25 V) among in vivo devices. Human breast model simulations and porcine skin experiments demonstrated that the delivery could reach a depth of 1 mm, supporting real-world application to human patients. Delivery of forkhead box M1 (FOXM1) siRNA by NEO-BRA on mice bearing TNBC tumors showed a significant tumor therapeutic effect, which reduced tumor growth by 2/3, programmed death-ligand 1 (PD-L1) expression by 3/4, and eliminated detectable lung metastasis, without invasiveness or toxicity. The NEO-BRA provides a bioelectronic interface for a novel neoadjuvant therapy of TNBC and other promising wearable tumor therapies.