Small but mighty: the versatility of nanobodies in modern medicine

Nanotools in biomedicine open up novel applications in research, diagnostics, and clinical care. Here, nanobody technology has emerged as a powerful platform, offering advantages over conventional antibodies due to their small size, high stability, and ability to target cryptic epitopes. Our review summarizes the structural and functional properties of nanobodies, their production and engineering strategies, and explores their expanding role in therapeutic applications. We discuss nanobody-based approaches in oncology, neurodegenerative and infectious diseases, as well as autoimmune disorders, focussing on their integration into molecular imaging, targeted drug delivery, and emerging modalities such as targeted protein degradation (TPD). Advances in nanobody engineering, including bispecific constructs, nanobody-drug conjugates, and intracellular targeting strategies, are accelerating their clinical translation. Despite challenges in manufacturing and regulatory approval, the approval of caplacizumab and ongoing clinical trials underscore the growing impact of nanobody therapeutics. With their versatility and potential for precision and personalized medicine, nanobody-based technologies drive innovation across biomedical research and next-generation therapies.