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Nanobody-drug conjugates (NDCs), which incorporate functional payloads (e.g., cytotoxic agents and immune agonists) into nanobodies, have attracted considerable attention in cancer therapy due to their unique ability to target cancer cells with high precision. This review analyzes the functional components of NDCs, including nanobodies, linkers, and payloads, and provides an integrated perspective on their molecular design, mechanisms of action, and clinical applications. The following four aspects are specifically emphasized: (i) the advantages and disadvantages of nanobodies as drug delivery carriers; (ii) current strategies to improve in vivo pharmacokinetic profiles; (iii) the development of multivalent and multispecific NDCs to enhance target engagement and address tumor heterogeneity; and (iv) the transition from conventional stochastic conjugation to highly homogeneous, site-specific conjugation strategies. These features provide a framework for understanding how NDC design can integrate selective delivery with programmable molecular engineering and may facilitate their future development for precision therapy.
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Sun et al. (2026) studied this question.
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