From conventional therapy to treatment with lipid-polymer hybrid nanoparticles for hepatocellular carcinoma

With unclear symptoms and ineffective therapies, hepatocellular carcinoma (HCC) is one of the deadliest types of cancer worldwide. Therefore, there is an urgent need to develop new diagnostic and therapeutic strategies that can overcome the limitations of currently used approaches. Cancer nanotechnology has been contributing to develop new platforms that allow the combination of multiple therapeutic and diagnostic agents, in order to create new, more effective and safer therapeutic approaches, as well as more assertive and precocious diagnoses. In this regard, lipid-polymer hybrid nanosystems have demonstrated to be able to efficiently and specifically deliver different therapeutic agents to target cells. These hybrid formulations bring together, in a single nanosystem, complementary characteristics of polymer-based and lipid-based nanoparticles, namely physical stability, biocompatibility, high drug loading capacity even for drugs with different physicochemical properties, long circulation times, capability of controlled drug release, targeting to specific cells and tissues, and superior in vivo efficacy and efficiency. In this review, we provide an extensive overview of the different types of lipid-polymer hybrid nanosystems and their main individual counterparts, as well as their potential to mediate new therapeutic strategies against HCC. Moreover, we also review the main molecular changes that occur in HCC, the current and the possible future treatment options, and the possible forms of active and passive targeting that could allow lipid-polymer hybrid nanosystems to achieve more effective and specific delivery in HCC, allowing the generation of a platform of knowledge for future treatments with greater efficacy and fewer side effects. • Lipid-polymer hybrid nanosystems to mediate efficient therapeutic strategies to HCC. • Identification of cell surface targets for active targeting of nanosystems to HCC. • Cell signaling pathways as source of molecular targets for new therapies. • Precision and multitarget nanomedicine as future HCC treatment.