Advances in Nanobody-Based Platforms for Precision Cancer Diagnosis and Therapy.

Nanobodies, single-domain antibodies derived from camelid heavy-chain antibodies, have emerged as powerful molecular tools in cancer diagnosis and therapy due to their unique structural and functional attributes, including small size, high antigen specificity, robust stability, and ease of genetic and chemical modification. This Review provides an extensive overview of the nanobody structure, characteristics, and production methods, highlighting their advantages over conventional antibodies. We comprehensively discuss various applications of nanobodies in cancer diagnosis and therapy, encompassing their roles as antagonists or agonists in modulating oncogenic and immune-related signaling pathways, targeted delivery systems for chemotherapeutics, radionuclides, immunotoxins, and photosensitizers, and their integration into advanced imaging technologies such as PET, SPECT, and optical imaging for accurate tumor detection and monitoring. Additionally, we explore the development of innovative cell-based immunotherapies leveraging nanobody-engineered chimeric antigen receptor (CAR)-modified T cells, natural killer cells, and macrophages, illustrating their potential to enhance therapeutic precision and efficacy. Finally, we discuss the current challenges and provide perspectives on emerging nanobody technologies and their translational prospects, underscoring the potential of nanobody-based toolkits to drive next-generation precision cancer diagnostics and therapies.