Active Targeting Design and Preclinical Progress of Liposome-Based Nanocarriers for Cancer Therapy

Cancer remains a critical threat to human health, yet its clinical treatments are severely hindered by multiple limitations, such as solid tumor physical barriers, poor drug solubility, short in vivo circulation half-life, acquired drug resistance, and non-targeted side effects. These challenges have underscored the urgency of developing advanced drug delivery systems to improve therapeutic efficacy and safety. This paper focuses on actively targeted nanoliposomes as a promising strategy to overcome the drawbacks of traditional cancer therapies and passive targeting liposomes. Unlike passive targeting relying on the EPR effect, actively targeted liposomes are modified with ligands (antibodies, aptamers, peptides, etc.) that specifically bind to overexpressed receptors on tumor cells, thereby enhancing tumor cell recognition, endocytosis, and drug accumulation at lesion sites while reducing normal tissue toxicity. The paper further outlines two major cellular entry pathways of these liposomes (membrane fusion and endocytosis) and highlights that carrier physical properties determine the dominant entry route. Additionally, it summarizes key bottlenecks in clinical translation, including long-term safety validation, blood-brain barrier penetration, antigen/receptor heterogeneity, and large-scale manufacturing, as well as corresponding optimization frameworks for scenario-based delivery, immunoliposome construction and industrialization. This paper provides a comprehensive reference for advancing the clinical application of actively targeted liposomes in cancer therapy.