Molecular Materials as Fluorescent Nano Gene Silencers: Peptide Gold Cluster as Promising Cancer Theranostics

The evasion of apoptosis, primarily by the overexpressed anti-apoptotic protein survivin, is a major challenge in cancer treatment. Here, we report a smart, multifunctional nano-gene silencing system designed to tackle this challenge. Our platform integrates ultrasmall (∼3 nm) red-emitting oligopeptide-stabilized gold nanoclusters (GNCs), functionalized with survivin-targeting siRNA and Her2-specific antibodies for selective, real-time monitored gene silencing therapy in breast cancer. The GNCs serve as highly fluorescent red-emitting imaging agents for real-time tracking. The positively charged oligopeptide ensures robust siRNA loading capacity. In SK-BR-3 breast cancer cells, the prepared nano system demonstrates enhanced cellular uptake and siRNA delivery when compared to commercial transfection agent Lipofectamine2000. The precise delivery resulted in potent knockdown of survivin and significant reduction in cell proliferation without triggering cytotoxicity. This work offers a streamlined and effective strategy to induce apoptosis and prevent tumor progression by targeting survivin. It positions our nanoplatform as a compelling candidate for next-generation, targeted cancer therapeutics with integrated diagnostic capability.