Antibody-DNA nanostructure conjugates exhibit inhibited effects on CT26 cells and prevent upregulation of PD-1 in the tumor microenvironment

Antibody drug conjugates (ADCs) offer targeted cancer therapy but face limitations in drug loading, stability, and immune modulation. Here, antibody DNA nanostructure conjugates (ADNCs) is reported as a next-generation platform that overcomes these challenges. By leveraging the programmable architecture of DNA nanostructures, ADNCs achieve high, tunable drug payloads without inducing antibody aggregation—a major drawback of conventional ADCs. In CT26 cells, gemcitabine-loaded ADNCs trigger dual cell death pathways—caspase-3-mediated apoptosis and RIP3-mediated necroptosis—enhancing tumor cell killing. In the CT26 syngeneic model, ADNCs suppress tumor growth with no observable toxicity and, notably, activate anti-tumor immunity without upregulating PD-1, suggesting avoidance of T-cell exhaustion. Critically, ADNCs maintain efficacy in patient-derived xenograft (PDX) models despite tumor heterogeneity. The study presents a novel, stable, and scalable antibody-drug conjugate (ADC)-inspired platform that integrates high payload delivery capacity with enhanced and adjustable drug-loading capabilities—characteristics that are seldom achieved in existing ADC technologies—thereby demonstrating translational potential for applications in precision oncology.