Surface Engineering of Lanthanide Nanoparticles for Oncotherapy

Surface-modified lanthanide nanoparticles have been widely developed as an emerging class of therapeutics for cancer treatment because they exhibit several unique properties. First, lanthanide nanoparticles exhibit a variety of diagnostic capabilities suitable for various image-guided therapies. Second, a large number of therapeutic molecules can be accommodated on the surface of lanthanide nanoparticles, which can simultaneously achieve combined cancer therapy. Third, multivalent targeting ligands on lanthanide nanoparticles can be easily modified to achieve high affinity and specificity for target cells. Last but not least, lanthanide nanoparticles can be engineered for spatially and temporally controlled tumor therapy, which is critical for developing precise and personalized tumor therapy. Surface-modified lanthanide-doped nanoparticles are widely used in cancer phototherapy. This is due to their unique optical properties, including large anti-Stokes shifts, long-lasting luminescence, high photostability, and the capacity for near-infrared or X-ray excitation. Upon near-infrared irradiation, these nanoparticles can emit ultraviolet to visible light, which activates photosensitizers and photothermal agents to destroy tumor cells. Surface modification with special ligands that respond to tumor microenvironment changes, such as acidic pH, hypoxia, or redox reactions, can turn lanthanide nanoparticles into a smart nanoplatform for light-guided tumor chemotherapy and gene therapy. Surface-engineered lanthanide nanoparticles can include antigens that elicit tumor-specific immune responses, as well as immune activators that boost immunity, allowing distant and metastatic tumors to be eradicated. The design of ligands and surface chemistry is crucial for improving cancer therapy without causing side effects. In this Account, we classify surface-modified lanthanide nanoparticles for tumor therapy into four main domains: phototherapy, radiotherapy, chemotherapy, and biotherapy. We begin by introducing fundamental bioapplications and then discuss recent developments in tumor phototherapy (photodynamic therapy and photothermal therapy), radiotherapy, chemotherapy, and biotherapy (gene therapy and immunotherapy). We also assess the viability of a variety of strategies for eliminating tumor cells through innovative pathways. Finally, future opportunities and challenges for the development of more efficient lanthanide nanoprobes are discussed.