Ultrasound-engineered chitosan nanocarriers improve the anticancer activity of dandelion phytochemicals in hepatocellular carcinoma cells

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Introduction HCC remains a leading cause of cancer-related mortality, with limited effective and safe treatment options. Although dandelion ( Taraxacum officinale )-derived phytochemicals show anticancer potential, their clinical use is restricted by poor solubility, instability, and low intracellular bioavailability. Ultrasound-engineered chitosan nanocarriers represent a promising strategy to overcome these limitations and enhance intracellular delivery. Accordingly, this study aimed to develop an ultrasound-assisted chitosan nanoparticle formulation encapsulating dandelion extract (UA-ChNPs/DE) to improve therapeutic efficacy against HCC cells. Methods UA-ChNPs/DE nanoparticles were synthesized using an ultrasound-assisted ionic gelation method. Physicochemical properties were characterized using dynamic light scattering, SEM, and XRD. The in vitro release behavior was assessed over 72 h. Cytotoxic activity was evaluated in hepatocellular carcinoma cell lines (HepG2 and Huh7) and normal hepatic (LO2) cells using a cell viability assay, while apoptosis induction in HepG2 cells was analyzed by flow cytometry. Results The optimized UA-ChNPs/DE exhibited a nanoscale particle size (∼105 nm), a narrow size distribution (PDI = 0.268), and a positive surface charge (+28.4 mV), indicating colloidal stability. Structural analysis confirmed successful encapsulation and partial amorphization of the phytochemical constituents. The nanoformulation demonstrated sustained release over 72 h with a reduced initial burst release compared with the free extract. Biological evaluation revealed significantly enhanced antiproliferative activity, with UA-ChNPs/DE achieving lower IC 50 values in HepG2 (17.8 μg/mL) and Huh7 (21.5 μg/mL) cells compared with the free extract (49.4 and 54.8 μg/mL, respectively). In normal LO2 cells, reduced cytotoxicity (IC 50 = 52.4 μg/mL) and higher selectivity index values (2.94 and 2.54) indicated preferential targeting of cancer cells. Additionally, UA-ChNPs/DE significantly increased apoptotic cell populations (∼40%), confirming enhanced apoptosis-mediated anticancer activity. Conclusion UA-ChNPs effectively overcome key physicochemical and pharmacokinetic limitations of dandelion-derived compounds, resulting in improved anticancer efficacy, sustained-release behavior, and preferential cytotoxicity toward hepatocellular carcinoma cells. This nanoformulation represents a promising strategy for advancing plant-derived therapeutics in HCC.