Alginate-driven nanotherapeutics in liver cancer: design, applications, and future perspectives

Liver cancer remains the most frequently diagnosed cancer worldwide and the leading cause of cancer-related mortality, accounting for approximately 2.2 million new cases and 1.8 million deaths annually. Despite advances in diagnosis and therapy, poor prognosis, late detection, and treatment-associated toxicity continue to limit clinical outcomes. Recent progress in nanotechnology has opened new avenues for overcoming these limitations through targeted and controlled drug delivery systems. This review critically examines the emerging role of alginate-based nanocarriers as versatile platforms for anticancer therapy, with particular emphasis on their design, fabrication strategies, and therapeutic mechanisms. Alginate, a naturally derived, biocompatible, and biodegradable polysaccharide, offers unique advantages such as mild gelation, tunable physicochemical properties, and responsiveness to tumor-specific stimuli. The review highlights a broad spectrum of alginate-engineered nanostructures, including nanoparticles, nanogels, microspheres, nanocapsules, micelles, and hybrid nanocomposites, demonstrating enhanced drug loading, tumor targeting, and reduced systemic toxicity. Mechanistic insights into enhanced permeability and retention (EPR)-mediated accumulation, pH-responsive release, mitochondrial targeting, and apoptosis induction are discussed. Furthermore, current challenges related to scalability, reproducibility, and clinical translation are addressed, alongside future perspectives for optimizing alginate-driven nanotherapeutics. Overall, alginate-based nanocarriers represent a promising and adaptable strategy for next-generation cancer therapy.