Colloidal hollow mesoporous
silica nanoparticles (HMSNs) are aspecial type of
silica-based nanomaterials with penetrating mesopore channels on their shells. HMSNs exhibit unique structural characteristics useful for diverse applications: Firstly, the hollow interiors can function as reservoirs for enhanced loading of guest molecules, or as nanoreactors for the growth of nanocrystals or for catalysis in confined spaces. Secondly, the mesoporous
silica shell enables the free diffusion of guest molecules through the intact shell. Thirdly, the outer
silica surface is ready for chemical modifications, typically via its abundant Si-
OH bonds. As early as 2003, researchers developed a soft-templating methodto prepare hollow
aluminosilicate spheres with penetrating mesopores in a cubic symmetry pattern on the shells. However, adapting this method for applications on the nanoscale, especially for biomedicine, has proved difficult because the soft templating
micelles are very sensitive to liquid environments, making it difficult to tune key parameters such as dispersity, morphology and structure. In this Account, we present the most recent developments in the tailored construction of highly dispersive and monosized HMSNs using simple
silica-etching chemistry, and we discuss these particles' excellent performance in diverse applications. We first introduce general principles of
silica-etching chemistry for controlling the chemical composition and the structural parameters (particle size, pore size, etching modalities, yolk-shell nanostructures, etc.) of HMSNs. Secondly, we include recent progress in constructing heterogeneous, multifunctional, hollow mesoporous
silica nanorattles via several methods for diverse applications. These elaborately designed HMSNs could be topologically transformed to prepare hollow mesoporous
carbon nanoparticles or functionalized to produce
HMSN-based composite nanomaterials. Especially in biomedicine, HMSNs are excellent as carriers to deliver either hydrophilic or hydrophobic anti-
cancer drugs, to
tumor cells, offering enhanced chemotherapeutic efficacy and diminished toxic side effects. Most recently, research has shown that loading one or more anticancer drugs into HMSNs can inhibit
metastasis or reverse multidrug resistance of
cancer cells. HMSNs could also deliver hydrophobic
perfluorohexane (PFH) molecules to improve high intensity focused ultrasound (HIFU)
cancer surgery by changing the tissue acoustic environment; and HMSNs could act as nanoreactors for enhanced catalytic activity and/or durability. The versatility of
silica-etching chemistry, a simple but scalable synthetic methodology, offers great potential for the creation of new types of
HMSN-based nanostructures in a range of applications.