Nanotechnology-driven biomaterials for chronic liver diseases: Stage-specific strategies for advanced theranostics.

Abstract

Chronic liver diseases (CLDs), encompassing a spectrum from steatosis and inflammation to fibrosis, cirrhosis, represent a major global health burden, causing approximately 2 million deaths annually [1]. The management of CLDs is significantly hampered by the limitations of conventional approaches, including non-targeted drug delivery, systemic toxicity, and inadequate diagnostic sensitivity for early-stage lesions. Nanotechnology-driven biomaterial platforms have emerged as pioneering solutions to these challenges, enabling precise theranostic strategies tailored to the distinct pathophysiology of each disease stage. This review systematically elaborates on these advancements by aligning with the natural progression of CLDs [non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis B, liver fibrosis, and cirrhosis]. We detail how engineered platforms enhance therapeutic efficacy by achieving superior hepatic accumulation, controlled drug release, and improved metabolic, antiviral, and antifibrotic effects. Concurrently, we explore their role in diagnostics, where nanotechnology-enhanced imaging agents and nanosensors provide unprecedented sensitivity for early detection and accurate staging. By structuring the discussion around the evolving clinical needs from NAFLD and hepatitis to advanced fibrosis and cirrhosis, this review offers a stage-specific roadmap of biomaterial design principles. It aims to provide a foundational theory and forward-looking perspectives for developing next-generation, precision medicine solutions for CLDs, ultimately bridging the gap between benchtop innovation and clinical translation. STATEMENT OF SIGNIFICANCE: This review establishes a stage-specific design paradigm that bridges the gap between biomaterial innovation and the clinical continuum of chronic liver diseases (CLDs). Its significance lies in aligning cutting-edge biomaterial strategies from targeted, stimuli-responsive nanotherapeutics to engineered exosomes and gene delivery systems with the distinct pathophysiological features of each disease stage. This approach moves beyond cataloging materials to critically evaluating their translational feasibility. We analyze how rational material design addresses specific clinical bottlenecks, such as improving drug bioavailability to diseased tissue or enabling sensitive, non-invasive diagnostics for early detection. By providing this clinically focused roadmap, this review aims to accelerate the development of personalized therapies and reshape the theranostic landscape, striving to improve therapeutic outcomes of CLDs.