Nanocomposites to Overcoming Sorafenib Resistance in Hepatocellular Carcinoma Therapy

The emergence of drug resistance is the major obstacle to the clinical application of sorafenib (SOR), which often leads to disease progression, recurrence, and even death in hepatocellular carcinoma (HCC) patients. Nanocomposite-mediated drug delivery enhances targeting precision and therapeutic utilization efficiency. Nanocomposites constructed by nanoparticles (NPs) and various therapeutic components have emerged as effective approaches to enhance HCC therapeutic efficacy. Designing based on the mechanisms underlying SOR resistance, specially engineered nanocomposites can be designed to overcome SOR resistance. This review aims to highlight the advantages of nanocomposites in overcoming HCC SOR resistance. First, the various SOR resistance mechanisms that have been identified so far are briefly outlined. Second, the construction methods and characteristics of nanocomposites designed to overcome SOR resistance are summarized and categorized according to different types of NPs. Subsequently, the roles and therapeutic effects of nanocomposites in SOR-resistant HCC are analyzed, primarily including remodeling the tumor microenvironment (TME), restoring normal epigenetic regulation, improving drug metabolism, and inhibiting abnormally activated signaling molecules and pathways. Finally, the advantages and disadvantages of nanocomposites used to reverse drug resistance are discussed, and their development direction in future research is prospected, which provide new approaches for developing advanced nanocomposites to overcome SOR resistance.