In cancer treatment, it is critical to enhance drug delivery efficiency to the target area while minimizing the side effects of chemotherapeutic drugs. Although intravenous administration of anticancer agents is commonly used, it often results in blood vessel damage and systemic side effects as well as poor targeted delivery. Therefore, developing new drug delivery formulations is essential to improve anticancer efficacy while reducing side effects. Herein, a nanohybrid methodology is presented to improve the targeted delivery of doxorubicin (DOX) for treating hepatocellular carcinoma (HCC) and to minimize vascular damage. An albumin-glucosamine (AG) lipid complex (LC), composed of stearyl glycyrrhetinate (SG) and DSPE-PEG, is designed to serve as a liver cancer-specific delivery system. The nanohybrid formulation, SGLC/DOX@AG, demonstrates significant anticancer activity and reduced side effects, as demonstrated by in vitro, in vivo, and cancer-on-a-chip models. This study presents a novel carrier design and application model for drug formulation development and efficacy validation, providing insights into therapeutic development for HCC.

A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed via attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. In vivo studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics.