Multishelled Hollow Silica Nanospheres with Programmable Encapsulation and Tumor-Responsive Catalytic Activities

Multishelled hollow silica nanospheres (HSNs) have emerged as a promising class of hierarchical nanostructures for applications in tumor therapy, cascade catalysis, and biomedical engineering, owing to their large surface areas, tunable architecture, and spatial compartmentalization. Here, we present a one-pot strategy based on a water-in-oil reverse microemulsion system for the scalable synthesis of multishelled HSNs with precise control over shell number, thickness, intershell spacing, and particle size (sub-100 nm), alongside in situ surface PEGylation for enhanced colloidal stability. This approach enables the production of high-yield, uniform single-shelled HSNs and structurally customizable variants with up to four concentric shells. MnOx-doped double-shelled HSNs exhibit tumor microenvironment-responsive catalytic activity, including hydrogen peroxide-driven oxygen generation and macrophage polarization, highlighting their relevance in immunomodulatory cancer therapy. Furthermore, spatially resolved encapsulation of hydrophilic (Au, Ag) and hydrophobic (FeOx) nanoparticles within discrete compartments demonstrates the platform’s capacity for compartmentalized loading, supporting applications in cascade catalysis and sequential drug delivery. By overcoming key limitations in scalability, dispersibility, and functional integration, this work establishes a robust and versatile nanofabrication framework for the development of next-generation silica-based nanocarriers in therapeutic and catalytic domains.