One-Step Synthesis of Cagelike Hollow Silica Spheres with Large Through-Holes for Macromolecule Delivery.

A facile, one-step method to prepare cagelike hollow silica nanospheres with large through-holes (HSNLs) using a lysozyme-assisted O/W miniemulsion technique is presented. The tetraethoxysilane (TEOS)-xylene mixture forms oil droplets which are stabilized by the cationic surfactant cetyltrimethylammonium bromide (CTAB), cosurfactant hexadecane (HD), and protein lysozyme. HSNLs (with diameter of 300-460 nm) with large through-holes (10-30 nm) were obtained directly after ultrasonic treatment and aging. Lysozyme can not only stabilize the oil/water interface, assist the hydrolysis of TEOS, and interact with silica particles to assemble into silica-lysozyme clusters but also contribute to the formation of through-holes due to its hydrophilicity variation at different pH conditions. A possible new mechanism called the interface desorption method is proposed to explain the formation of the through-holes. To confirm the effectiveness of large through-holes in delivering large molecules, bovine serum albumin (BSA, 21 × 4 × 14 nm3 ) was chosen as a model guest molecule; HSNLs showed much higher loading capacity compared with common hollow mesoporous silica nanospheres (HMSNs). The release of BSA can be well controlled by wrapping HSNLs with a heat-sensitive phase change material (1-tetradecanol). Cell toxicity was also conducted with a Cell Counting Kit-8 (CCK-8) assay to roughly evaluate the feasibility of HSNLs in biomedical applications.