Next-Generation Nanocarriers for Hematological Malignancies: A Mechanistic Review of Stimuli-Responsive and Targeted Delivery Systems

Leukemia management has improved with the advent of tyrosine kinase inhibitors and immunotherapy; however, long-term remission remains limited due to relapse, systemic toxicity, and the persistence of leukemic stem cells (LSCs) within the bone marrow niche. Conventional therapies often fail to effectively target these protected microenvironments, leading to drug resistance and disease recurrence. This review summarizes recent advances (2010–2025) in nanocarrier-based strategies for leukemia treatment, focusing on organic, inorganic, and hybrid nanoplatforms. Particular emphasis is placed on targeted delivery systems that utilize ligand-mediated recognition of leukemia-associated markers such as CD33, CD123, and CD26, along with microenvironment-responsive drug release mechanisms. Organic nanocarriers, including liposomes, polymeric micelles, and dendrimers, enhance drug solubility, stability, and pharmacokinetics while reducing off-target toxicity. In contrast, inorganic nanomaterials such as gold and iron oxide nanoparticles offer multifunctional capabilities, including imaging and stimulus-responsive therapeutic delivery. Emerging biomimetic systems further improve immune evasion and bone marrow targeting by mimicking natural cellular components. Collectively, these nanotechnology-driven approaches provide a promising platform for improving therapeutic precision and overcoming current limitations in leukemia treatment. Despite challenges related to scalability, regulatory approval, and long-term safety, continued integration of nanotechnology with molecular oncology may facilitate the development of more effective and targeted therapies for hematological malignancies.