• Nanobodies in Medical Biotechnology; Applications and Advances in Therapeutic and Diagnostic Innovations
  • Tahereh Rezazadeh,1,* Roghaye Arezumand,2 Mona Fani,3 Sara Nemati,4
    1. Department of Advanced Sciences and Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
    2. Department of Advanced Sciences and Technologies, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
    3. Department of Pathobiology & Laboratory Sciences, School of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran
    4. Department of Biology, East Tehran Branch, Islamic Azad University, Tehran, Iran


  • Introduction: Nanobodies, also known as single-domain antibodies (sdAbs), are a relatively new class of antibody fragments that are derived from heavy-chain-only antibodies naturally found in Camelidae species. These small, robust molecules have become powerful tools in medical biotechnology due to their unique structural and functional properties. Their small size (~15 kDa), high stability, and ability to bind to epitopes that conventional antibodies cannot access make nanobodies particularly well-suited for a wide range of therapeutic and diagnostic applications. This unique structure not only enhances their stability and solubility but also enables the engineering of bispecific and multispecific formats, expanding their potential in complex therapeutic scenarios. Additionally, their ease of production in microbial systems allows for large-scale manufacturing, making them attractive alternatives to conventional antibodies. Nanobodies are generated through immunization of Camelidae species or via phage display technology, where a large library of synthetic nanobodies is screened for binding to a specific antigen. The selected nanobodies are then characterized for their binding affinity, specificity, and stability. Nanobodies can be conjugated with drugs, toxins, or radioisotopes to target specific cells, such as cancer cells, with high precision for therapeutic applications. In diagnostic applications, nanobodies can be linked to fluorescent, radioisotope, or enzymatic markers to detect biomarkers in various diseases, including infectious diseases, cancer, and neurological disorders.
  • Methods: The terms “Nanobodies and their applications” were searched in PubMed, Science Direct, and Google Scholar, the selected articles were critically evaluated.
  • Results: Promising results have emerged from preclinical and clinical trials for nanobody-based therapeutics. For illustration, nanobody-drug conjugates have demonstrated heightened targeting of cancer cells with reduced off-target effects, resulting in enhanced efficacy and safety profiles. Nanobodies have been integrated into various diagnostic tools, such as biosensors and imaging methods, delivering exceptional sensitivity and specificity in detecting disease biomarkers. Moreover, their diminutive size and capacity to penetrate biological barriers like the blood-brain barrier make nanobodies an attractive option for treating disorders of the central nervous system, opening up new avenues for research and development.
  • Conclusion: Nanobodies exhibit superior tissue penetration due to their small size, enabling them to effectively target solid tumors and other hard-to-reach areas. This is because they can bind to unique epitopes, including those in enzyme active sites or those hidden within protein complexes, which further enhances their utility in both therapeutic and diagnostic applications. Furthermore, the ease of genetic manipulation allows for the development of multifunctional nanobody constructs, such as multispecific nanobodies, which can simultaneously target multiple antigens and improve treatment outcomes in complex diseases. Despite these advantages, challenges remain, particularly with regard to the immunogenicity of nanobodies in humans. Although they originate from camelids, which could potentially trigger immune responses, strategies such as the humanization of nanobodies and the use of human-derived nanobody libraries are being explored to mitigate this issue. Additionally, the development of resistance to nanobody-based therapies, as observed with other biologics, is an area that requires ongoing research and monitoring. Nanobodies represent a transformative innovation in medical biotechnology, offering significant advantages over traditional antibodies for both therapeutic and diagnostic applications. Their small size, high stability, and ability to access unique epitopes make them ideal candidates for a wide range of medical applications, ranging from targeted drug delivery to sensitive diagnostic assays. Continued research and development in this field is expected to further enhance the utility of nanobodies, address current challenges, and expand their role in precision medicine.
  • Keywords: Nanobodies, single-domain antibodies, medical biotechnology, therapeutic applications, drug delivery