Lanthanide-based nanoparticles for cancer phototherapy

Phototherapy, using light as a therapeutic modality, has been widely applied in treating various diseases, especially cancer. This approach is valued for its non-invasive nature and minimal risk of drug resistance. However, phototherapy faces challenges such as the undesired delivery of phototherapeutic agents, potential phototoxicity, and limited penetration of light into tissues. Lanthanide-doped nanoparticles offer attractive opportunities to improve the therapeutic efficacy of photodynamic therapy. These nanoparticles are distinguished by their unique optical properties, such as excellent photostability against blinking and bleaching effects, large Stokes or anti-Stokes shifts, sharp emission peaks, and long luminescence lifetimes. In addition, lanthanide-doped nanoparticles can be excited by near-infrared (NIR) light or X-rays, enabling deep-tissue penetration. Beyond the use of photosensitizers, nanoparticle surfaces can be easily modified with targeting ligands, chemical drugs, or functional molecules to enhance the effectiveness of phototherapy or to enable combination therapy. In this review, we organize the use of lanthanide-based nanoparticles in tumor phototherapy into six main domains: photodynamic therapy, photothermal therapy, X-ray-based therapy, light-controlled therapy, photoimmunotherapy, and other innovative treatments that can be regulated by light. We introduce the basic principles of phototherapy and the characteristics of lanthanide nanoparticles. Following this, we summarize the latest advances in utilizing lanthanide-based nanoparticles for tumor phototherapy, focusing on their design principles, mechanisms of action, and effectiveness in cancer treatment. To conclude, we address the existing challenges and explore future opportunities within this area of research.