Silica Coated Upconversion Nanoparticles: A Versatile Platform for the Development of Efficient Theranostics

Next generation theranostic devices will rely on the smart integration of different functional moieties into one system. These individual chemical elements will have a variety of desired chemical and physical properties and will need to behave in a multifunctional manner. Researchers have used upconversion nanoparticles (UCNPs) as a basis for superior imaging probes to locate cancerous lesions. The features of these nanoparticles, such as large anti-Stokes shifts, sharp emission bands, long-lived luminescence, and high resistance to photobleaching, have produced versatile probes. One way to improve these probes is to add a layer of dense or mesoporous silica to the outer surface of UCNPs (UCNP@SiO2). These modified UCNPs are chemically stable and much less cytotoxic than the original UCNPs. In addition, their surface can be easily modified to introduce various functional groups (e.g., -NH2, -COOH, -SH) via silanization, which facilitates conjugations with various biological molecules for multimodal imaging or synergetic therapeutics. This versatility makes UCNP@SiO2 particles excellent platforms for the construction of efficient theranostics. In this Account, we provide a comprehensive summary of recent progress in the development of UCNP@SiO2 nanocomposites for theranostics in the hope of speeding their translation into the clinic. We first discuss the major design principles and protocols for engineering various nanocomposites based on UCNP@SiO2 structures including those coated with dense silica, mesoporous silica, or hollow mesoporous silica. Next we summarize several representative efforts that probe the relaxivity mechanisms of these nanostructures as a way to optimize magnetic resonance sensitivity, multimode cancer imaging, near-infrared light-triggered chemotherapy, photodynamic therapy, and synergetic therapy (the combination of radiotherapy with chemotherapy, thermotherapy, or photodynamic therapy) using UCNP@SiO2-based theranostics. By rational integration of a wide range of features that convey multiple functions (such as imaging and therapy) into the structure or onto the surfaces of UCNP@SiO2, the constructed theranostics show promise for multimodal cancer imaging, biosensing, and effective cancer therapy. Finally, we discuss the limitations of UCNP@SiO2 nanostructures, the difficulties in the design of smart theranostics, and their potential role in clinical cancer research.