NIR-II luminescent rare-earth-doped nanomaterials for precision targeted and surgical navigation of tumors

Abstract

Rare-earth ion (Ln³⁺)-doped nanomaterials (NMs) have garnered significant attention in the biomedical field owing to their deep-tissue penetration and outstanding spatial resolution in the second near-infrared window (NIR-II, 1000–1700 nm). By conjugating functional molecules such as peptides and small molecules, these NMs can integrate multiple targeting mechanisms, including passive and active targeting, which are of great significance for precise targeting and theranostics of malignant cancers. In this review, we first provide a comprehensive overview of the synthesis strategies of Ln³⁺-doped NMs, highlighting the advantages, limitations, and applicability of various approaches. It then discusses in detail the luminescence mechanisms of Ln³⁺ ions in the NIR-II region, as well as recent advances in emission enhancement strategies and in vivo NIR-II imaging modalities. Subsequently, we summarize the cutting-edge applications of functionalized Ln³⁺-doped NMs in passive targeting, active targeting, physicochemical targeting, and biomimetic nanostructures. Moreover, we analyze their utility in clinical navigation across different scenarios, including small tumor detection, tumor margin delineation, and sentinel lymph node mapping. Finally, we present a forward-looking perspective on future research directions, focusing on key challenges such as improving absorption cross-sections, ensuring biosafety, validating efficacy in large-animal models, and exploring specific biological targets.