A Nanoplatform of Reversing Tumor Immunosuppressive Microenvironment Based on the NIR-II Gold Hollow Nanorod for the Treatment of Hepatocellular Carcinoma

Abstract

Advanced hepatocellular carcinoma (HCC) presents a strongly immunosuppressive tumor microenvironment, which enables tumor cells to evade immune cell attacks and hinder effective drug killing, thereby hindering the achievement of the desired therapeutic effect. In response, a novel nanoplatform- AuHNR@γ-Fe₂O₃@Lenvatinib@β-Glucan (AFLG) with surface modified β-1,3-glucan is developed, which exhibits potent immunostimulatory effect and the capability of repolarizing macrophages, to counteract the immunosuppressive conditions present in the tumor microenvironment. Leveraging the hollow structure of gold nanorods, Lenvatinib is efficiently loaded, a first-line targeted drug for HCC, which effectively inhibits tumor angiogenesis. Additionally, through atomic layer deposition, γ-Fe₂O₃ is generated on the hollow gold nanorod surface, endowing it with chemodynamic therapy and magnetic resonance T₂-weighted imaging capabilities while excellently maintaining the gold nanorod's superior photothermal therapy and photoacoustic imaging properties under 1064 nm excitation. These AFLG NPs feature dual-modal imaging and quadruple-modal synergistic therapy capabilities, along with their powerful potential in remodeling the immunosuppressive tumor microenvironment, offering an encouraging novel approach for the treatment of hepatocellular carcinoma.