Stimuli-responsive liposomes and niosomes in leukemia therapy: targeted delivery and clinical translation.

Leukemia, a heterogeneous group of hematologic malignancies, remains a therapeutic challenge due to drug resistance, systemic toxicity, and poor specificity of conventional treatments. In recent years, nanocarrier-based drug delivery systems particularly liposomes (phospholipid bilayers enabling hydrophilic/hydrophobic drug encapsulation) and niosomes (non-ionic surfactant vesicles offering stability and controlled release) have gained attention for their ability to overcome these limitations. This review comprehensively explores the design, formulation, and functionalization of these carriers tailored for leukemia therapy. Emphasis is placed on their roles in drug encapsulation (doxorubicin, cytarabine) and gene delivery (siRNA, plasmids). Mechanistically, these nanocarriers enable targeted delivery via ligand/receptor interactions, passive targeting through enhanced permeability and retention (EPR) effect, and stimuli-responsive release (pH, redox, enzyme-sensitive systems), thereby improving bioavailability and reducing off-target toxicity. Furthermore, co-delivery systems are discussed for their synergistic potential in combination therapies. Challenges including scalability, immunogenicity, and formulation stability are critically analyzed, alongside regulatory hurdles hindering clinical translation. The review also examines emerging trends, such as smart nanocarriers, personalized nanomedicine, and the integration of AI and biosensors for precision therapy. By highlighting both current advances and future directions, this article underscores the transformative role of liposomal and niosomal nanocarriers in reshaping leukemia treatment paradigms and moving toward safer, more effective, and patient-tailored therapeutic strategies. However, key challenges such as drug resistance, relapse, treatment-associated toxicity, and the high cost of novel therapies remain significant barriers. Future perspectives focus on integrating precision medicine, optimizing combination therapies, and advancing translational research to improve long-term survival and quality of life for patients with acute leukemia.