Figure 4.
pH/ROS-responsive capability and synergistic antitumor effect with chemotherapy in vitro. (a) Cumulative release of iron ions from Lp-IO at pH 7.4 and 6.5 (n = 3). (b) Cumulative release of DOX from DOX@Lp-IO at pH 7.4 and pH 6.5 (± 1 mM H2O2) and from DOX@Lp at pH 6.5 (+ 1 mM H2O2) (n = 3). (c and d) 4T1 cells were treated with RhB6G@Lp-IO&Dio and stained with LysoTracker™ Blue and MitoTracker™ Deep Red (n = 5). (c) PCC analysis of the FL signals. (d) Merged FL images of 4T1 cells at 3 and 6 h; scale bar: 20 μm. (e) Viability of cancer cells (4T1 and U87) and normal cells (L-02 and HUVEC) treated with DOX@Lp and DOX@Lp-IO for 24 h. (f) IC50 and CI for Lp-IO, DOX@Lp and DOX@Lp-IO. Additive effect (CI = 1), synergism (CI < 1) and antagonism (CI > 1). (g) Relative cellular uptake of DOX@Lp and DOX@Lp-IO based on the intracellular DOX contents. (h) Relative xCT expression and GPX-4 activity in 4T1 cells treated with PBS (NC), DOX, Lp-IO or DOX@Lp-IO (n = 3). (i) Synergistic mechanism of Lp-IO and DOX released from DOX@Lp-IO. *: compared with NC. *, P < 0.05; **, P < 0.01.