Nanotechnology Enhanced RNAi Therapies in Cancer: A Systematic Review

Cancer remains a major cause of illness and death worldwide, with conventional treatments often hindered by systemic toxicity, lack of specificity, and the development of resistance. RNA interference (RNAi) provides a highly targeted approach to silencing cancer-causing genes and disrupted signalling pathways, laying the groundwork for precision cancer treatment. Although it holds great promise, clinical use of RNAi is currently limited by poor stability, rapid breakdown in the blood, limited cell uptake, entrapment in endosomes, and barriers within the tumour microenvironment. Nanotechnology-based delivery systems have become a key strategy for overcoming these challenges, enhancing RNAi stability, promoting targeted tumour accumulation, facilitating efficient cell internalisation, and enabling controlled release within cells. This review provides a comprehensive assessment of the biological basis of RNAi, the obstacles to its effective use, and the various types of nanocarriers developed to improve therapeutic outcomes. Combination approaches combining RNAi with chemotherapy, immunotherapy, and gene editing are also explored, alongside advances in passive and active tumour targeting. A summary of preclinical and clinical data proving the pharmacokinetic benefits, safety, and effectiveness of nanocarrier-assisted RNA interference is provided.  Finally, new developments, including patient-specific RNAi treatments, biodegradable and intelligent nanomaterials, and integration with biomarker-driven tactics, are emphasised. This review highlights the revolutionary potential of RNA interference (RNAi) enhanced by nanotechnology for safe, accurate, and efficient cancer treatment, while also pointing to directions for further translational research.