Ultrasound-Triggered Albumin Nanoparticles Deliver Glycyrrhetinic Acid and Nitric Oxide Against Liver Cancer

An open-access study published in Cancer Nanotechnology on 24 August 2026 reports the development of an ultrasound-assisted albumin nanoparticle system co-loaded with glycyrrhetinic acid and nitric oxide, designated SNO-HSA-GA, for the synergistic treatment of hepatocellular carcinoma. The work addresses two well-known obstacles: glycyrrhetinic acid shows potent anti-HCC activity but dissolves poorly in water, limiting its clinical use, while nitric oxide becomes cytotoxic to tumor cells at high concentrations. Combining both agents in one carrier, the authors argue, allows each compound to contribute to tumor killing within a single formulation.

The optimized formulation measured an average particle size of 232.4 ± 6.2 nm with a zeta potential of -31.2 ± 1.5 mV and achieved a glycyrrhetinic acid loading of 11.86 ± 1.05%. In vitro release testing showed a pH-dependent drug release pattern that was further enhanced when ultrasound stimulation was applied, meaning the acoustic trigger could in principle be used to control when and where the payload is liberated from the nanoparticles.

In laboratory assays with hepatoma cells, SNO-HSA-GA significantly inhibited cell viability, migration, and colony formation, while showing minimal toxicity toward normal hepatocytes. Mechanistic investigations indicated that ultrasound-triggered nitric oxide release activated the p53/p21 signaling axis, downregulated expression of CDK4, CDK6, and cyclin D1, and induced cell-cycle arrest in the G0/G1 phase. These molecular changes offer a proposed explanation for how the co-loaded particles suppress tumor cell proliferation in culture.

In vivo experiments described in the study demonstrated efficient tumor accumulation, local nitric oxide release, substantial inhibition of tumor growth, and increased apoptosis without systemic toxicity when SNO-HSA-GA was combined with ultrasound irradiation. The authors conclude that SNO-HSA-GA represents a promising nanoplatform for synergistic HCC therapy. As with any preclinical nanomedicine platform, these findings come from cell and animal models reported in the article’s abstract, and clinical translation would require further validation; the published version is an early-shared, peer-reviewed accepted manuscript subject to final edits.

Subject of Research: Ultrasound-assisted glycyrrhetinic acid and nitric oxide co-loaded albumin nanoparticles for hepatocellular carcinoma therapy

Article Title: Ultrasound-assisted glycyrrhetinic acid/nitric oxide co-loaded albumin nanoparticles for the synergistic treatment of hepatocellular carcinoma

Article References: Tong, Q., Xi, J., Shi, X., Shao, Y., Jiang, X., Shi, T., Pan, X., Liu, S., Yang, H., & Zhuang, R. X. (2026). Ultrasound-assisted glycyrrhetinic acid/nitric oxide co-loaded albumin nanoparticles for the synergistic treatment of hepatocellular carcinoma. Cancer Nanotechnology. https://doi.org/10.1186/s12645-026-00420-y

Image Credits: AI Generated

DOI: 10.1186/s12645-026-00420-y

Keywords: hepatocellular carcinoma, albumin nanoparticles, glycyrrhetinic acid, nitric oxide, ultrasound-triggered release, drug delivery, p53/p21 signaling, cell-cycle arrest, nanomedicine, Cancer Nanotechnology, Ultrasound-assisted, glycyrrhetinic