Small but mighty: the versatility of nanobodies in modern medicine

Nanobodies, the single-domain fragments derived from camelid antibodies, are increasingly recognized as a transformative class of biomolecules. Their compact size, exceptional stability, and ability to access otherwise hidden epitopes provide clear advantages over conventional antibodies. These properties have enabled applications ranging from molecular imaging and diagnostics to targeted drug delivery and intracellular protein modulation. After decades of development, nanobody-based therapeutics are now moving into the clinic, with the approval of caplacizumab marking an important milestone in their medical relevance.

This review highlights the structural and functional features that make nanobodies uniquely versatile, alongside recent engineering strategies that expand their scope. Advances such as bispecific formats, nanobody–drug conjugates, and intracellularly active variants are opening new opportunities in oncology, neurodegenerative, infectious, and autoimmune diseases. Looking ahead, integration with cutting-edge modalities including targeted protein degradation, CAR-T cell therapy, and gene editing points to their potential to address previously “undruggable” targets. Although challenges remain in delivery, manufacturing, and regulatory approval, rapid progress in AI-driven design, high-throughput display technologies, and smart delivery systems is paving the way for next-generation nanobody therapeutics. Together, these developments position nanobodies as powerful tools at the forefront of precision medicine and future biologics.