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 <em>in vivo</em> 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 FOXM1 siRNA by NEO-BRA on mice bearing TNBC tumors showed a significant tumor therapeutic effect, which reduced tumor growth by 2/3, 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.