(A–B) Schematic of the treatments. (A) Mice bearing two, contralateral ~5 mm diameter 9464D tumors were treated on one tumor (designated “primary” tumor) with either vehicle (PBS), PBNP, CpG-PBNP, PBNP-PTT or CpG-PBNP-PTT and the contralateral tumor (designated “secondary” tumor) was left untreated. (B) The the vehicle group received 50 μL of PBS i.t., the PBNP-treated group received 50 μL of 1 mg mL−1 PBNPs i.t, the CpG-PBNP-treated group received 50 μL of 1 mg mL−1 CpG-PBNPs i.t, the PTT-treated groups received 50 μL of 1 mg mL−1 PBNPs or CpG-PBNPs i.t., and were irradiated with an 808 nm laser for 10 minutes at a temperature maintained at 120 °C. Additionally, the CpG-PBNP and CpG-PBNP-PTT groups received two boosters with CpG-PBNP on days 2 and 5. The dosage of CpG for these two groups was 2 μg of CpG conjugated onto PBNP on days 0, 2, and 5 i.t. (C–D) Temperature versus time profiles (C) and thermal doses administered expressed in cumulative equivalent minutes at 43 °C (log(∑CEM43)) (D) of 9464D tumor-bearing mice treated i.t. with 50 μL of 1 mg mL−1 CpG-PBNPs or PBNPs and irradiated with a NIR laser at 120°C for 10 minutes. 0.15 mg mL−1. (E) Tumor growth curves of “primary” tumors of 9464D tumor-bearing mice that were treated with (a) PBS, (b) PBNP, (c) CpG-PBNP, (d) PBNP-PTT, or (e) CpG-PBNP-PTT. (F) Tumor growth curves of “secondary” tumors of 9464D tumor-bearing mice that were treated with (a) PBS, (b) PBNP, (c) CpG-PBNP, (d) PBNP-PTT, or (e) CpG-PBNP-PTT. (G) Aggregated tumor growth curves of primary tumors of 9464D TH-MYCN murine model of NB that were treated with PBS, PBNP, CpG-PBNP, PBNP-PTT, or CpG-PBNP-PTT on the primary tumor side. (H) Aggregated tumor growth curves of secondary tumors of 9464D TH-MYCN murine model of NB that were treated with PBS, PBNP, CpG-PBNP, PBNP-PTT, or CpG-PBNP-PTT on the primary tumor side.(I) Kaplan–Meier survival plots of 9464D tumor bearing mice that were treated with CpG-PBNP-PTT, PBNP-PTT, PBNP, CpG-PBNP or vehicle (PBS). Results are expressed as mean ± std. deviation; (n=5); *p < 0.05 (with respect to CpG-PBNP), **p < 0.01, ****p < 0.0001 (ANOVA).