Bioinspired Diffusion-Limited Silicification in Coacervate Assemblies Enables Smart Nanotoroids for Deep and Sensitive Tumor Penetration

Controlling the self-assembly of mesoporous materials beyond equilibrium remains a fundamental challenge. Conventional templating systems form ordered structures through energy-minimizing coassembly but lack the kinetic and spatial freedom required to produce asymmetric or topologically complex architectures. Here, we report a bioinspired coacervate-directed silicification strategy that enables diffusion-limited and spatially asymmetric condensation within soft templates, yielding ordered hexagonal mesoporous nanotoroids. In this system, poly(acrylic acid) (PAA) electrostatically associates with the cationic surfactant cetyltrimethylammonium bromide (CTAB), driving liquid-liquid phase separation and forming disc-like coacervate assemblies. Reaction-diffusion imbalance across the inner and outer interfaces within these templates induces asymmetric silicification, driving an interior collapse and toroidal self-transformation. By tuning PAA concentration, the diffusion-condensation kinetics can be precisely modulated, allowing programmable control over collapse dynamics and final topology, with enlarged central cavities (14-71 nm) and reduced rim thickness (15-35 nm). These nanotoroids exhibit uniform sub-100 nm size, high surface area (846 m² g^-1), and abundant mesopores (∼2.0 nm). The nanotoroids (rim thickness ∼15 nm, height ∼40 nm) display markedly prolonged blood circulation, enhanced tumor accumulation (+173%), improved vascular extravasation, and deeper intratumoral penetration, while reducing hepatic and splenic uptake by 19% and 14%, respectively, compared with spherical analogues. These combined advantages translate into potent antitumor efficacy in both subcutaneous and spinal metastasis models. This work establishes a new paradigm for sol-gel topology control by bridging reaction-diffusion dynamics with bioinspired silicification based on the chemistry of LLPS (liquid-liquid phase separation), thereby unlocking the untapped biomedical potential of toroidal topologies that were rarely accessible.