Anisotropic gold nanochains with dual-ligand interfaces for theranostic immune activation.

Antibody-dependent cellular cytotoxicity (ADCC) represents a key mechanism of cancer immunotherapy, yet conventional antibody-nanoparticle systems often suffer from limited Fc accessibility, random ligand orientation, and short circulation stability. To overcome these limitations, we developed a modular gold nanochain platform through end-to-end assembly of alkyne- and azido-functionalized gold nanorods using click chemistry. Each nanorod unit was selectively modified with folic acid or immunoglobulin G (IgG) Fc fragments to achieve spatially segregated tumor-targeting and immune-engaging functionalities. The resulting polyethylene glycol (PEG)-linked nanochains exhibited tunable length, excellent colloidal stability, and characteristic plasmonic coupling, enhancing both surface-enhanced Raman scattering (SERS) and near-infrared absorption. Cellular studies using folate receptor-positive KB cells confirmed receptor-mediated uptake and selective binding, while ADCC assays demonstrated significantly enhanced natural killer (NK) cell-mediated cytolysis compared to single nanorods and even the monoclonal antibody control (Herceptin). Mechanistically, the elongated morphology and multivalent Fc presentation facilitated stable immune synapse formation and improved effector cell recruitment. Collectively, this study establishes a versatile and biocompatible nanochain platform that integrates cancer targeting, immune activation, and optical imaging within a single construct, offering a promising direction for next-generation immunotheranostic nanomedicine.