Cell viability

Following digestion with 0.25% EDTA-free trypsin (cat. no. C0205; Shanghai Biyuntian Biotechnology Co., Ltd.), the NCI-H446 and M059K cells were separately counted and adjusted to a cell suspension of 5×10⁴ cells/ml. Subsequently, 100 µl cell suspension was transferred to each well of a 96-well cell culture plate and cultured for 24 h. After discarding the old culture medium, 100 µl NCI-H446 cells (or M059K cells) were treated with IONP (0.7 µg/ml), PTX (0.3 µg/ml), IONP (0.7 µg/ml) + PTX (0.3 µg/ml), and XTP@PNOI (1.0 µg/ml) at 37°C for 24 h. Simultaneously, untreated cells were set as a negative control. Thereafter, 10 µl Cell Counting Kit-8 solution (cat. no. KGA317; Nanjing KeyGen Biotech Co., Ltd.) was added to each well and incubated for another 2 h. After shaking gently for 10 min, the optical density (OD) of each well was detected at 450 nm on a microplate reader (BioTek ELx800; BioTek) and cell growth inhibitory rate was calculated using the formula: Inhibitory rate (%)=[(OD of control group-OD of experimental group)/(OD of control group-OD of blank group)] ×100. As shown in a previous study (57), the calculation formula of drug interaction was calculated using the following formula: combination index=E_a+b/(E_a + E_b-E_a × E_b), where a and b are any two treatments, E_a+b is the inhibitory rate of the combined a and b treatments, and E_a and E_b are separately the inhibitory rates of a and b. A combination index between 0.85 and 1.15 shows an additive effect and its value >1.15 shows synergistic interactions.