Fig. 5

Exo-Lut-NPs sensitizing hepatoma cells to sorafenib by regulating HSCs on the HepG2/LX2 sorafenib-resistant model in vitro. A Schematic illustration of the establishment of the HepG2/LX2 sorafenib-resistant model in vitro. Created with https://www.biorender.com/. Based on the model, the effects of the Exo-Lut-NPs on reversing sorafenib resistance to HepG2 cells via LX2 cells were investigated. B Hemolytic test of different concentrations of Exo-Lut-NPs. The hemolysis percentages were assessed 1 h after adding different concentrations of Exo-Lut-NPs. Erythrocytes treated with PBS (0% hemolysis) and distilled water (100% hemolysis) were used as controls. No obvious hemolysis was observed up to 1 mg/ml of Exo-Lut-NPs (n = 3, mean ± SD). C Culture medium (CM) of LX2 after treated with PBS or sorafenib at different concentrations was collected, including a control group (PBS-CM) and other model groups (8 μM Sorafenib-CM, 20 μM Sorafenib-CM and 25 μM Sorafenib-CM). The effects of different CM on HepG2 resistance to sorafenib were investigated by measuring the cell viability of HepG2 cells after exposure to 19.5 μM sorafenib, aiming to determine the optimum resistance-induced concentration of sorafenib on LX2 cells (n = 5, mean ± SD). D Effects of the CM of LX2 after treated with free luteolin (20 μM) (Free Lut-CM) on sorafenib resistance of HepG2 were investigated based on the in vitro HepG2/LX2 sorafenib-resistant model (n = 5, mean ± SD). E Effects of CM of LX2 cells treated with (i) HepG2 exosomes (Exo-CM), (ii) PLGA-NPs without loading luteolin (PLGA-NPs-CM), (iii) free luteolin (20 μM Free Lut-CM), (iv) Lut-NPs (Lut-NPs-CM), and v) Exo-Lut-NPs (Exo-Lut-NPs-CM) on HepG2 resistance to sorafenib were investigated, respectively. The PBS-CM group was a control group and 20 μM Sorafenib-CM was a model group (n = 3, mean ± SD). NS: Not Significant, **P < 0.01, ***P < 0.001, ****P < 0.0001