Lanthanide ion (Ln(3+))-based upconversion nano/micromaterials that emit higher-energy visible light when excited by low-energy NIR light have aroused considerable attention in the forefront of materials science and biomedical fields, which stems from their unique optical and chemical properties including minimum photodamage to living organisms, low autofluorescence, high signal-to-noise ratio and detection sensitivity, and high penetration depth in biological or environmental samples. Thus, Ln(3+)-based upconversion materials are rising new stars and are quickly emerging as potential candidates to revolutionize novel biomedical applications. In this review article, we mainly focus on the recent progress in various chemical syntheses of Ln(3+)-based upconversion nanomaterials, with special emphasis on their application in stimuli-response controlled drug release and subsequent therapy. Functional groups that are introduced into the stimuli-responsive system can respond to external triggers, such as pH, temperature, light, and even magnetic fields, which can regulate the movement of the pharmaceutical cargo and release the drug at a desired time and in a desired area. This is crucial to boost drug efficacy in cancer treatment while minimizing the side effects of cytotoxic drugs. Many multifunctional (magnetic/upconversion luminescence and porous) composite materials based on Ln(3+) have been designed for controlled drug delivery and multimodal bioimaging. Finally, the challenges and future opportunities for Ln(3+)-based upconversion materials are discussed.

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging, and therapy in one nanostructured matrix to construct multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. In this work, a facile methodology is developed to construct a multifunctional anticancer drug nanocarrier by combining the special advantages of upconversion nanoparticles and mesoporous silica. β-NaYF4 :Yb(3+) , Er(3+) @β-NaGdF4 :Yb(3+) is chosen as it can provide the dual modality of upconversion luminescence and MRI. Then mesoporous silica is directly coated onto the upconversion nanoparticles to form discrete, monodisperse, highly uniform, and core-shell structured nanospheres (labeled as UCNPs@mSiO2 ), which are subsequently functionalized with hydrophilic polymer poly(ethylene glycol) (PEG) to improve the colloidal stability and biocompatibility. The obtained multifunctional nanocomposites can be used as an anticancer drug delivery carrier and applied for imaging. The anticancer drug doxorubicin (DOX) is absorbed into UCNPs@mSiO2 -PEG nanospheres and released in a pH-sensitive pattern. In vitro cell cytotoxicity tests on cancer cells verify that the DOX-loaded UCNPs@mSiO2 -PEG has comparable cytotoxicity with free DOX at the same concentration of DOX. In addition, the T1 -weighted MRI that measures in aqueous solutions reveals that the contrast brightening increases with the concentration of Gd(3+) component. Upconversion luminescence images of UCNPs@mSiO2 -PEG uptaken by cells show green emission under 980 nm infrared laser excitation. Finally, the nanocomposites show low systematic toxicity and high in vivo antitumor therapy efficacy. These findings highlight the fascinating features of upconversion-mesoporous nanocomposites as multimodality imaging contrast agents and nanocarrier for drug molecules.

Incorporating the agents for magnetic resonance imaging (MRI), optical imaging and therapy in one nanostructured matrix to construct a multifunctional nanomedical platform has attracted great attention for simultaneous diagnostic and therapeutic applications. A facile methodology is reported by J. Lin and co‐workers to construct a multifunctional nanocarrier composed of individual luminescent/magnetic β‐NaYF4:Yb3+, Er3+@β‐NaGdF4:Yb3+ directly coated with mesoporous silica, followed by functionalization with poly(ethylene glycol), which can act as an effective platform for upconversion luminescence and magnetic resonance dual‐modal imaging and in vivo anticancer drug delivery.