Asymmetric single-hole mesoporous silica nanocages, which are eccentric hollow structured spheres and consist of mesoporous shell with an open hole on their surface, with uniform particle size (100-240 nm), have successfully been synthesized via a novel anisotropic encapsulation of the mesoporous silica. In this unique nanocarrier, the eccentric hollow cavity and big hole (∼25 nm) can serve as a storage space and passage for large guest molecules. Meanwhile, the uniform mesopores (2-10 nm) with a high surface area (∼500 m(2)/g) in the silica shells of the nanocages can provide storage space for small guest molecules. The obtained single-hole mesoporous nanocages can be endowed upconversion luminescence. The obtained upconversion nanoparticles functionalized eccentric single-hole nanorattles were used to codeliver bovine serum albumin and doxorubicin dual-sized guests. The release of the dual-sized guests can be well controlled independently by heat and near-infrared (NIR) light with the assistance of NIR to ultraviolet/visible (UV/vis) optical properties of upconversion nanoparticles and heat-sensitive phase change materials.