Nanobody: a promising toolkit for molecular imaging and disease therapy

Abstract

Nanobodies are the recombinant variable domains of heavy-chain-only antibodies, with many unique properties such as small size, excellent solubility, superior stability, quick clearance from blood, and deep tissue penetration. As a result, nanobodies have become a promising tool for the diagnosis and therapy of diseases. As imaging tracers, nanobodies allow an early acquisition of high-quality images, provide a comprehensive evaluation of the disease, and subsequently enable a personalized precision therapy. As therapeutic agents, nanobodies enable a targeted therapy by lesion-specific delivery of drugs and effector domains, thereby improving the specificity and efficacy of the therapy. Up to date, a wide variety of nanobodies have been developed for a broad range of molecular targets and have played a significant role in patients with a broad spectrum of diseases. In this review, we aim to outline the current state-of-the-art research on the nanobodies for medical applications and then discuss the challenges and strategies for their further clinical translation.

Keywords: Cancer; Inflammation; Molecular imaging; Nanobody; Therapy.

Fig. 1

Schematic illustration of mAb, HcAb, nanobody, and multivalent nanobody. (a) The application of nanobodies, it has a favorable role for imaging and therapy. (b) Classical mAb is composed of two identical light (L) chains and heavy (H) chains. Each heavy or light chain contains two functional domains, i.e., variable region (VR) and one constant region (CR). The difference is that light chain has only one constant region, whereas heavy chain has three or four constant regions. (c) HcAb naturally lacks light chains and CH1 domains. Its variable fragment is the nanobody. (d) Nanobody consists of four framework regions and three complementarity-determining regions. (e) Nanobodies can be produced in a bivalent format, either bivalent-monospecific or bivalent-bispecific. Furthermore, the addition of a third nanobody that binds to serum albumin (anti-Alb) can form multivalent constructs; all these formats can prolong the half-life of nanobodies in the bloodstream

Fig. 2

Nanobody-based targeted disease therapy. Owing to their superior target specificity and binding affinity, nanobodies often serves as targeting moieties and brings effector domains or drugs to lesions of interest, including radionuclide (a), drugs (b), toxins(c), and fusion peptides (d)