Supramolecular Spherical Polyelectrolyte Brushes on Gold Nanoparticles for Light-Triggered Gene Delivery

Spherical polyelectrolyte brushes (SPBs) have been of great interest in biomedicine, particularly in gene delivery, yet their brush architectures are commonly fixed, showing limited tunability and responsiveness. Herein, we report a light-controllable supramolecular SPB (AuNP@CDs@Azo-PD) constructed by assembling azobenzene-terminated poly(2-(dimethylamino)ethyl methacrylate) (Azo-PD) onto β-cyclodextrin-functionalized gold nanoparticles (AuNP@CDs) via reversible host-guest interactions. The resulting nanostructure exhibits a core-shell architecture with a brush-like polymer corona. Characterization of the system through dynamic light scattering (DLS) and UV-vis spectroscopy confirmed the successful formation of the nanocarrier and its ability to undergo controlled structural transitions under UV irradiation. The SPB system was further evaluated for its gene delivery capability, showing excellent biocompatibility and effective plasmid DNA encapsulation, with protection against serum nucleases. In vitro transfection studies revealed that AuNP@CDs@Azo-PD achieved comparable transfection efficiency to Lipofectamine 3000, with efficient gene expression and suppression of the PI3K/AKT signaling pathway. Additionally, UV-triggered release of the PTEN gene resulted in enhanced tumor suppression effects, including reduced cell proliferation, migration, and increased apoptosis. These findings demonstrate the potential of AuNP@CDs@Azo-PD as a versatile and responsive nanoplatform for controlled gene delivery and cancer therapy.