Advances in ligand-targeted nanodelivery systems for leukemia therapy: from single- to dual-ligand strategies

BACKGROUND: Leukemia is a highly heterogeneous and aggressive hematological malignancy. Current therapeutic approaches (e.g. chemotherapy, radiotherapy, small-molecule targeted therapies, and hematopoietic stem cell transplantation, etc.) are widely limited in clinical practice by systemic drug toxicity, acquired drug resistance, off-target effects, and graft rejection, highlighting the urgent need for safer and more effective innovative treatment strategies. MAIN BODY: Ligand-targeted nanodelivery systems achieve precise recognition and targeted delivery to tumor cells by modifying the surface of nanocarriers with ligands (e.g. antibodies, aptamers, proteins, peptides, and small molecules, etc.). This review systematically summarizes common therapeutic targets in leukemia, existing treatment agents, and strategies for constructing ligand-functionalized nanocarriers, with a particular focus on the fundamental research and clinical progress of single-ligand and dual-ligand targeted delivery systems. Overall, most studies indicate that dual-ligand systems exhibit superior targeting efficiency and therapeutic performance compared with single-ligand systems; however, clinical translation still faces challenges, including large-scale manufacturing, immunogenicity and systemic toxicity evaluation, regulatory and intellectual property barriers, and the development of humanized models. CONCLUSIONS: Ligand-targeted nanodelivery systems have been applied in multiple areas of leukemia treatment, including drug delivery, gene therapy, and diagnostic detection. Future research should prioritize the development of combination therapeutic strategies, as well as the diversified application of nanomaterials in ligand modification and immunotherapy models; meanwhile, the integration of artificial intelligence to assist ligand design and optimization may provide new directions for further improving targeted therapeutic strategies for leukemia.