Morphology Evolution and Spatially Selective Functionalization of Hierarchically Porous Silica Nanospheres for Improved Multidrug Delivery

Hierarchically porous materials are believed one of the most promising matrix materials due to their unique multimodal pore structures and great application potentials in catalysis, separation, and biomedicine. In this article, a series of hierarchically porous silica nanospheres with adjustable morphologies and pore structures/sizes has been successfully developed by controlling the electrostatic interaction-induced interfacial self-assembly behaviors between anionic block copolymer polystyrene-b-poly­(acrylic acid) (PS-b-PAA), cationic surfactant cetyltrimethylammonium bromide, and tetraethyl orthosilicate. Especially, “embedded” structured dual-mesoporous silica nanospheres (E-DMSNs) containing connected large mesopores (>10 nm) and abundant small mesopores (2–3 nm) in the large-pore framework have been prepared for the first time. Moreover, by employing PS-b-PAA with shorter PAA block lengths as template, the morphology conversion of porous silica nanospheres from core–shell structured dual-mesoporous silica nanospheres to well-defined hollow mesoporous silica nanospheres has been achieved. To endow the capability of E-DMSNs as multidrug delivery vehicles, a spatially selective functionalization strategy has been adopted to obtain dual-functionalized E-DMSNs (E-DMSNs-NH₂/OH) with amino-functionalized large mesopores and hydroxyl-modified small mesopores. Thermogravimetric-differential scanning calorimetry analysis shows that the loading amount of curcumin (Cur) and doxorubicin hydrochloride (DOX) were about 3.4% and 10.0% in weight, respectively. In addition, the cytotoxicity assay and cellular uptake of DOX@Cur@E-DMSNs-NH₂/OH on SMMC-7721 cells (human hepatoma cells) have been investigated. Thus, such a simple methodology to synthesize hierarchically porous silica with adjustable morphologies, pore sizes, and pore modifications provides a new pathway for the rational design of antitumor multidrug nanocarriers in further cancer treatment.