Nanomaterials: An Innovative Integrative Paradigm for Hepatocellular Carcinoma Adjuvant Treatment

This review systematically examines the application of nanomaterials in adjuvant therapy for hepatocellular carcinoma (HCC) following surgical resection, with the aim of synergistically inhibiting tumor recurrence and driving functional liver regeneration via a 3R paradigm (removing residual tumor cells; remodeling the immune microenvironment; and repairing liver function). This article begins by analyzing the clinical challenges associated with treating HCC on the basis of global epidemiological data and the molecular characteristics of residual micrometastases after surgery. The concept of “precision space-time intervention" is then introduced, and the design strategies and clinical development of nanomaterials are explored, including targeting, biomimetic, sustained release and degradable designs. Furthermore, this review focuses on the postresection imbalance between tumor recurrence and tissue regeneration in the HCC microenvironment, elucidating the multiscale regulatory mechanisms of liver repair, such as cell differentiation, angiogenesis regulation, maintenance of the cellular redox balance, metabolic reprogramming, and modulation of the inflammatory microenvironment. The temporal dynamics of these mechanisms are emphasized, and the pivotal role of nanomaterials in this context is clarified. The key findings of this review indicate that a multimodal platform with nanomaterials as functional units can integrate diagnosis, hemostasis, antitumor activity and regeneration promotion, thereby overcoming the limitations of monotherapy, which cannot effectively cover the entire process of liver repair. This review breaks through the static intervention model of traditional adjuvant therapy, providing theoretical evidence for the development of multimodal sequential therapeutic nanoplatforms and outlining a clinical translation pathway from the validation of molecular mechanisms to GMP-standard production. Multimodal nanomaterials for the comprehensive restoration of liver function following hepatocellular carcinoma (HCC) surgery: Simultaneously promoting hepatic regeneration and inhibiting tumor recurrence (Created with Biorender.com).