Preclinical And Translational Applications of Nanoparticulate Drug Delivery System in Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally, with limited treatment options and poor prognosis for advanced stages. Nanoparticulate drug delivery systems (NDDS) have emerged as a promising therapeutic strategy, offering enhanced targeting, controlled release, and reduced off-target effects compared to traditional chemotherapeutic treatments. This review explores the preclinical and translational applications of NDDS in the treatment of HCC, focusing on the mechanisms by which nanoparticles improve drug delivery efficiency. Key nanoparticle types, including liposomes, polymeric nanoparticles, dendrimers, and metal nanoparticles, are discussed in terms of their formulation, advantages, and mechanisms of action such as the enhanced permeability and retention (EPR) effect, cellular uptake, and targeted release. Furthermore, the potential for combining NDDS with other therapeutic strategies, such as gene therapy, immunotherapy, and drug combinations, is examined to enhance treatment efficacy. Despite the promising results in preclinical models, significant challenges remain in the clinical translation of NDDS, including issues related to large-scale production, regulatory approval, biocompatibility, and long-term toxicity. Advances in nanoparticle engineering, including the development of multifunctional, biodegradable, and stimuli-responsive systems, are paving the way for overcoming these obstacles. This review highlights the current state of research and offers insights into the future prospects for the clinical application of NDDS in HCC treatment, emphasizing the importance of collaborative, multidisciplinary research to fully realize their potential in improving patient outcomes.