Liposomal nanotherapeutics for cancer treatment: Targeted delivery and immunotherapy

Cancer has become a major global health crisis and the second leading cause of death worldwide. With over 270 different types, it is estimated to claim 13 million lives by 2030. The complex pathophysiology of cancer, with its diverse genetic, epigenetic, and biochemical pathways, complicates the diagnostic criteria. Therapeutic approaches such as surgical interventions, radiotherapy, chemotherapy, and immunotherapy have been developed. However, the treatment is still challenging due to higher costs, toxicity, off-target effects, and comorbid conditions. Over the decades, liposomes, based on their particle size, surface charge, lipid composition, and lamellarity, have been explored for different therapeutic modalities for other cancers. They offer unique advantages, including improved drug efficacy, controlled site-specific release, enhanced cellular uptake, reduced systemic toxicity, and greater capacity to overcome tumor-induced resistance mechanisms. Researchers have explored liposomal treatment modalities for breast, lung, adenocarcinoma, ovarian, liver, fibrosarcoma, glioblastoma, and brain cancers. The tumor targeting drugs, for example, doxorubicin and paclitaxel, are delivered at the tumor microenvironment (TME) by passive and active transport, utilizing both the enhanced permeability and resistance (EPR) effect and cellular targets, for example, receptors, proteins, and organelles, in response to physical stimuli, for example, temperature, pH, fluid pressure, and nutrient and metabolic regulation. However, liposomes also face several limitations, including endosomal entrapment, heterogeneous targeting, suboptimal uptake by antigen-presenting cells (APCs), and storage instability. This review focuses on the advancements in liposomal nanocarriers for targeted cancer therapy. It emphasizes the evolution of their formulations to overcome potential limitations, making them highly tumor-specific and effective.