Advances in siRNA-loaded liposomes for lung cancer: Challenges and future perspectives

Lung cancer is the second most prevalent cancer worldwide. Despite significant progress in early diagnosis and therapy, it still stands as the leading contributor to cancer-related mortality worldwide. While different approaches for lung cancer treatment are currently adopted in clinical settings, lung tumors often exhibit resistance to these treatments, resulting in reduced survival rates. Small interfering ribonucleic acid (siRNA) provides a gene-based therapeutic option for cancer management, particularly when traditional therapies are ineffective, by silencing oncogenes and anti-apoptotic genes. Developing an effective delivery strategy for naked siRNAs requires overcoming in vivo challenges, including systemic exposure, poor stability, and the risk of eliciting an immune reaction. Liposomes offer promising approaches to these limitations, due to their excellent biocompatibility and ability to enhance siRNA delivery into tumor tissues through endocytosis and membrane fusion. This review showcases the importance of siRNA-loaded liposomal systems in lung cancer treatment, encompassing their recent applications in both preclinical and clinical studies. Although siRNA delivery systems in cancer therapy have been well-studied, few reviews specifically address the unique challenges and recent advances in siRNA-loaded liposomes for the treatment of lung cancer. Existing literature often takes a broad view or focuses on other types of cancer. This review aims to fill that gap by providing an up-to-date overview of formulation strategies and translational potential in this context. It explores the etiology of lung cancer and current therapies, along with their limitations, highlights the benefits of siRNA in treating lung cancer, and delves into the role of liposomes in advancing siRNA gene therapy, while addressing existing challenges.