Gold Nanoplatforms for Phenotypic Reprogramming and Closed-Loop Theranostics of Cancer Stem Cells

Conventional physical interventions, including static photothermal ablation, frequently fail to eradicate cancer stem cells (CSCs) and instead induce sublethal stress that promotes therapeutic resistance. To address this translational challenge, this review establishes a comprehensive framework utilizing engineered gold nanoplatforms to advance the treatment strategy from non-specific cytotoxicity toward mechanism-driven phenotypic reprogramming. We outline how stimuli-responsive surface functionalization helps resolve the size-permeability paradox to secure precise intracellular access. Upon internalization, these platforms suppress intrinsic defenses by intercepting morphogenic pathways, inducing mesenchymal-to-epithelial transitions, and disrupting the bioenergetic dependence of multidrug resistance. Following this phenotypic stabilization, gold nanostructures catalyze targeted cell death via ferroptotic redox disruption and dual-metabolic blockade, alongside the immunological remodeling of the tumor microenvironment. Ultimately, by integrating real-time metabolic feedback with macroscopic surveillance, this strategy highlights the potential of gold nanoplatforms as adaptive, responsive systems to achieve precision therapy and overcome CSC-driven relapse.