Nanobodies as Versatile Tool for Multiscale Imaging Modalities

Abstract

Molecular imaging is constantly growing in different areas of preclinical biomedical research. Several imaging methods have been developed and are continuously updated for both in vivo and in vitro applications, in order to increase the information about the structure, localization and function of molecules involved in physiology and disease. Along with these progresses, there is a continuous need for improving labeling strategies. In the last decades, the single domain antigen-binding fragments nanobodies (Nbs) emerged as important molecular imaging probes. Indeed, their small size (~15 kDa), high stability, affinity and modularity represent desirable features for imaging applications, providing higher tissue penetration, rapid targeting, increased spatial resolution and fast clearance. Accordingly, several Nb-based probes have been generated and applied to a variety of imaging modalities, ranging from in vivo and in vitro preclinical imaging to super-resolution microscopy. In this review, we will provide an overview of the state-of-the-art regarding the use of Nbs in several imaging modalities, underlining their extreme versatility and their enormous potential in targeting molecules and cells of interest in both preclinical and clinical studies.

Highly synergistic combinations of nanobodies that target SARS-CoV-2 and are resistant to escape

“…Beyond typical administration methods, a major advantage of nanobodies is their potential for direct delivery by nebulization deep into the lungs ( Wölfel et al, 2020 ; Nambulli et al, 2021 ). This route can provide a high local concentration in the airways and lungs to ensure rapid onset of therapeutic effects, while limiting the potential for unwanted systemic effects ( Erreni et al, 2020 ) as exemplified by clinical trials ( Van Heeke et al, 2017 ; Zare et al, 2021 ). Moreover, with respect to deployment, nanobodies are relatively inexpensive and easy to reproducibly manufacture, with long shelf-lives and greater inherent stability compared to other biologicals, including monoclonals.…”

Structural Insights into the Design of Synthetic Nanobody Libraries

“…Although naïve libraries do not either require immunization, the procedure is complex and involves animals. In particular, to obtain a library similar in size to a typical synthetic library, a few liters of blood collected from at least 10 animals is required [ 7 , 60 , 61 ].…”

Nanobodies: from structure to applications in non-injectable and bispecific biotherapeutic development

“…Many excellent reviews provided excellent information and perspectives on the applications of nanobodies, including their applications in the study of the structures and functions of G protein-coupled receptors (GPCRs), 9 molecular imaging, 10 biosensing, 11 tumor diagnosis, 12 CAR-T therapy, 13 and the development of therapeutics against cancer and infectious diseases. 14,15 However, the structural basis of nanobodies for these applications has not been fully discussed.…”