OH-Rich Interfacial Nanoarchitectonics for the Reconciliation of Structural Stability and Functional Accessibility in Curcumin Nanotherapeutics

Curcumin offers significant therapeutic potential but is hindered by poor aqueous stability and limited cellular accessibility. Here, we present a curcumin nanotherapeutic platform featuring OH-rich, silanol-rich porous silica nanointerfaces (CU@silica NPs) that successfully decouple structural stabilization from molecular mobility. By employing poly(allylamine hydrochloride) (PAH)-assisted assembly and rapid tetramethyl orthosilicate (TMOS) hydrolysis, we engineered a mesostructured silica shell with a high density of surface silanol groups, creating diffusion pathways that preserve curcumin mobility while protecting it from degradation. This permeable nanointerface enables lipid-triggered fluorescence activation, allowing activation-responsive monitoring of drug delivery. The OH-rich silica interface further ensures exceptional redispersibility and functional preservation even after repeated powderization cycles, a critical requirement for long-term storage and transport. Supported by molecular dynamics simulations and in vitro evaluations, CU@silica NPs demonstrate accelerated cellular uptake and a five-fold improvement in anticancer efficacy compared with CU NPs. These findings establish silica nano-interface engineering as a robust strategy for developing storage-stable, stimuli-responsive, and image-guided nanomedicines for hydrophobic drugs.