Advance of nanobody drug conjugates (NDCs) for cancer therapy

Antibody-drug conjugates (ADCs) have garnered significant attention in both academia and industry due to their outstanding potential in cancer treatment. The design principle is to precisely deliver highly toxic payloads to target cancer cells, thereby maximizing therapeutic efficacy while minimizing toxicity to normal cells as much as possible. In recent years, nanobody-drug conjugates (NDCs) have emerged as a superior alternative to ADCs, offering advantages such as enhanced stability, multi-functionality, improved tissue penetration, rapid clearance and low immunotoxicity. These properties position NDCs as promising candidates for next-generation cancer therapeutics. In this review, we first provide a brief overview of the structural differences between ADCs and NDCs, and subsequently focus on the multiple structural forms of NDCs that have been developed over the past two decades. The purpose of this article is to offer updated insights into the latest NDC platforms, thereby expanding the range of effective and safe treatment options for cancer patients and guiding the development of novel NDC-based therapeutics.