In vivo anticancer efficacy. Tumor growth curves
(a) and survival curves (d) of MC38 tumor-bearing C57BL/6 mice after
indicated treatments, n = 6. Tumor growth curves
(b) and survival curves (e) of CT26 tumor-bearing BALB/c mice after
indicated treatments, n = 6. Tumor growth curves
(c) and survival curves (f) of KPC tumor-bearing C57BL/6 mice after
indicated treatments, n = 5. PBS, OxPt plus IRI,
OxPt NCP, ZnP/SN38, or OxPt/SN38 was intravenously dosed once every
3 days with 3.5 mg/kg OxPt or and 6.2 mg/kg SN38 equiv to the MC38
model (eight doses) and CT26 and KPC models (six doses). A 75 μg
portion of anti-PD-L1 antibody (αPD-L1) was i.p. injected in
the same dosing schedule. (g) H&E staining and TUNEL IHC staining
of excised MC38 tumors at the end point. Scale bars: 100 μm.
Photo (h) and ratios of genitourinary tract weights versus total body
weights (i) of TRAMP mice treated with PBS, OxPt plus IRI plus αPD-L1,
OxPt/SN38, or OxPt/SN38 plus αPD-L1 at an equivalent dose of
3.5 mg/kg OxPt and/or 6.2 mg/kg SN38 Q3D for ten doses, n = 4. MC38-OVA-luciferase luminescence intensities (j), survival
curves (k), and in vivo imaging (l) of C57BL/6 mice
with liver metastases at different time points. Seven days after injection
of MC38-OVA-luciferase cells into the spleens, mice were treated with
PBS, OxPt plus IRI plus αPD-L1, OxPt/SN38, or OxPt/SN38 plus
αPD-L1 at an equivalent dose of 3.5 mg/kg OxPt and/or 6.2 mg/kg
SN38 Q3D for 5 doses, n = 5. (m) Representative images
of H&E staining of livers of C57BL/6 mice with liver metastases
at the end point. Scale bars: 100 μm. Data are expressed as
means ± SD. The data were analyzed by Student’s two-tailed t test (a, b) or one-way analysis of variance (ANOVA; c,
i–k). *p < 0.05, **p <
0.01, ***p < 0.001, ****p <
0.0001. A log-rank (Mantel–Cox) test was used for statistical
analysis of survival curves.