Fig. 7

Potent antitumor activity of the combination of DOX@3D-MPs and anti-PD-1 antibody. a Schematic timeline for the antitumor experiments in H22, 4T1 and Panc02 tumor-bearing mice after administration of six doses of PBS or DOX@3D-MPs derived from H22 TRCs, 4T1 TRCs and Pan02 TRCs at DOX dosage of 0.75 mg kg⁻¹ once every other day with or without of intraperitoneal injection of anti-PD-1 antibody at the dosage of 5 mg kg⁻¹ every 4 days for three times, respectively. b, d Tumor volume curves of H22 (b) and 4T1 tumor-bearing mice (d) after treatments indicated in a. (n = 8 mice in each group). c, e, i Kaplan-Meier survival plots of H22 (c), 4T1 (e) and Panc02 tumor-bearing mice (i) after treatments indicated in (a) (n = 10 mice in each group for (c) and n = 8 mice in each group for (e and i)). f Tumor weights of Panc02 tumor-bearing mice at 11 days after treatments indicated in (a). (n = 8 mice in each group). g, h Numbers (g) and representative images (h) of intestine metastatic nodes in Panc02 tumor-bearing mice at 11 days after treatments indicated in (a). (n = 8 mice in each group for (g)). Scale bar: 10 mm for (h). j–l Numbers of CD8⁺Ki67⁺ T (j), CD8⁺IFN-γ⁺ T (k) and CD8⁺GzmB⁺ T cells (l) in tumor tissues of H22 tumor-bearing mice at 11 days after treatments indicated in a by flow cytometry. (n = 6 mice in each group). m, n Numbers of CD8⁺CD44⁺CD62L⁺ T (m) and CD8⁺CD44⁺CD62L^- T cells (n) in the blood of naïve mice, DOX@3D-MPs- or DOX@3D-MPs+anti-PD-1 antibody-cured H22 tumor-bearing mice indicated in a by flow cytometry. (n = 10 for naive mice, n = 3 and 9 for DOX@3D-MPs- and DOX@3D-MPs+anti-PD-1 antibody-cured mice, respectively). o, p Tumor volume curves of naive mice, DOX@3D-MPs- or DOX@3D-MPs+anti-PD-1 antibody-cured H22 tumor-bearing mice indicated in (a) after rechallenge with H22 (2 × 10⁶ cells) (o) and 4T1 (p) cells (5 × 10⁵ cells). (n = 10 for naive mice, n = 3 and 9 mice for DOX@3D-MPs- and DOX@3D-MPs+anti-PD-1 antibody-cured groups, respectively). q–s Percentages of Ki67⁺ (q), IFN-γ⁺ (r) and GzmB⁺ cells (s) in CD8⁺ T cells from H22 cell debris-restimulated splenocytes of naïve mice, DOX@3D-MPs- or DOX@3D-MPs+anti-PD-1 antibody-cured H22 tumor-bearing mice indicated in (a) by flow cytometry. (n = 10 for naive mice, n = 3 and 9 mice for DOX@3D-MPs- and DOX@3D-MPs+anti-PD-1 antibody-cured groups, respectively). t Cytotoxicity of T cells (effector cells) against H22 cells (target cells) at 24 h after T cells isolated from H22 cell debris-restimulated splenocytes of naive mice, DOX@3D-MPs- or DOX@3D-MPs+anti-PD-1 antibody-cured H22 tumor-bearing mice treated as indicated in (a) were incubated with H22 cells at different effector/target ratios by LDH assay. (n = 3). Data are shown as means ± s.d. *P < 0.05, **P < 0.01, ***P < 0.001