Near-infrared (NIR)-to-visible up-conversion fluorescent nanoparticles have potential to be used for photodynamic therapy (PDT) in deep tissue because NIR light can penetrate thick tissue due to weak absorption in the optical window. Here a uniform layer of mesoporous silica is coated onto NaYF(4) up-converting nanocrystals, with a large surface area of approximately 770 m(2) g(-1) and an average pore size of 2 nm. A photosensitizer, zinc phthalocyanine, is incorporated into the mesoporous silica. Upon excitation by a NIR laser, the nanocrystals convert NIR light to visible light, which further activates the photosensitizer to release reactive singlet oxygen to kill cancer cells. The photosensitizer encapsulated in mesoporous silica is protected from degradation in the harsh biological environment. It is demonstrated that the photosensitizers loaded into the porous silica shell of the nanoparticles are not released out of the silica while they continuously produce singlet oxygen upon excitation by a NIR laser. The nanoparticles are reusable as the photosensitizers encapsulated in the silica are removed by soaking in ethanol.