Nanobody-nanocarrier systems for targeted drug delivery in cancer therapy

Nanobodies are compact single-domain antibody fragments distinguished by their high stability, tissue-penetrating ability, and ease of molecular engineering. As the smallest naturally occurring antigen-binding domains, they have considerable potential as targeting ligands for precision drug delivery. In parallel, nanocarriers, such as micelles, liposomes, lipid nanoparticles, extracellular vesicles, dendrimers, and inorganic nanoparticles, have been extensively investigated to improve the solubility, stability, pharmacokinetics, and biodistribution of therapeutic payloads. Although conventional antibodies and antibody-derived fragments have been widely studied for nanocarrier functionalization, nanobody-functionalized nanocarriers remain comparatively underexplored. Emerging studies suggest that the compact size, structural stability, and versatile conjugation chemistry of nanobodies can facilitate controlled nanocarrier functionalization while preserving target accessibility and binding activity. In this review, we systematically examine nanobody-nanocarrier systems for targeted drug delivery, with primary emphasis on cancer therapy and selected applications in other diseases. The targets are categorized as cell-surface receptors, immune checkpoints and immune cell markers, tumor-associated antigens, stromal and barrier-associated molecules, and soluble mediators. We further discuss how nanobody functionalization affects nanocarrier accumulation, receptor-mediated uptake, intracellular trafficking, target-associated signaling, and therapeutic efficacy. Finally, we highlight key challenges related to conjugation control, ligand density, pharmacokinetics, immunogenicity, manufacturing, and clinical translation. By integrating recent and representative studies, this review identifies emerging design considerations and future opportunities for developing nanobody-functionalized nanocarriers as precise and versatile drug-delivery systems.

Abstract from PubMed (PMID 42984425). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.